Safe Handling of Boranes at Scale

Atkins, William J.; Burkhardt, and Elizabeth R.; Matos, Karl

doi:10.1021/op068011l

Cited by 46 publications

(48 citation statements)

References 26 publications

(18 reference statements)

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“…Although many borohydride reagents are relatively stable solids, their contact with moisture can cause decomposition with the release of hydrogen gas. Therefore, appropriate precautions are required for larger scale reactions as well as during transport and storage [5]. …”

Section: Introductionmentioning

confidence: 99%

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

Lamm¹,

Pan²,

Taniguchi³

et al. 2013

Beilstein J. Org. Chem.

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SummaryAcetic acid promotes the reduction of aldehydes and ketones by the readily available N-heterocyclic carbene borane, 1,3-dimethylimidazol-2-ylidene borane. Aldehydes are reduced over 1–24 h at room temperature with 1 equiv of acetic acid and 0.5 equiv of the NHC-borane. Ketone reductions are slower but can be accelerated by using 5 equiv of acetic acid. Aldehydes can be selectively reduced in the presence of ketones. On a small scale, products are isolated by evaporation of the reaction mixture and direct chromatography.

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Section: Introductionmentioning

confidence: 99%

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

Lamm¹,

Pan²,

Taniguchi³

et al. 2013

Beilstein J. Org. Chem.

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“…1 3,4-Difluoro-2-methylbenzoic Acid (15). A 50 L jacketed reactor was flushed with nitrogen and charged with magnesium turnings (852 g, 35 mol) followed by a few crystals of iodine (0.2 g) and 2-methyltetrahydrofuran (2-MeTHF) (20 L).…”

Section: Methodsmentioning

confidence: 99%

“…Care was taken not to heat the reaction mixture in order to eliminate the risk of formation of diborane. 15 When the imide had been completely consumed, methanol was added slowly over a period of 16−24 h to ensure that the liberated hydrogen was efficiently removed. Calorimetric evaluation ( Figure 5) showed that the hydrogen evolution was mostly complete after the addition of the first 10% of the charge of the methanol and was generally controlled by the rate of addition ( Figure 6).…”

Section: Imide-based Synthesis Of Bromobenzoxazepinementioning

confidence: 99%

Process Development and Scale-Up of a Benzoxazepine-Containing Kinase Inhibitor

Naganathan

Andersen

et al. 2015

Org. Process Res. Dev.

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The benzoxazepine core is present in several kinase inhibitors, including the mTOR inhibitor 1. The process development for a scalable synthesis of 7-bromobenzoxazepine and the telescoped synthesis of 1 are reported. Compound 1 consists of three chemically rich, distinct fragments: the tetrahydrobenzo[f ][1,4]oxazepine core, the aminopyridyl fragment, and the substituted (methylsulfonyl)benzoyl fragment. Routes were developed for the preparation of 3-fluoro-2-methyl-4-(methylsulfonyl)benzoic acid (17) and tert-butyl 7-bromo-2,3-dihydrobenzo[f ][1,4]oxazepine-4(5H)-carboxylate (2). The processes for the two compounds were scaled up, and over 15 kg of each starting material was prepared in overall yields of 42% and 58%, respectively. A telescoped sequence beginning with compound 2 afforded 7.5 kg of the elaborated intermediate 5-(2,3,4,5-tetrahydrobenzo[f ][1,4]oxazepin-2-amine dihydrochloride (6) in 63% yield. Subsequent coupling with benzoic acid 17 gave 7.6 kg of the target compound 1 in 84% yield. The preferred hydrochloride salt was eventually prepared. The overall yield for the synthesis of inhibitor 1 was 21% over eight isolated synthetic steps, and the final salt was obtained with 99.7% HPLC purity.

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“…The Schiff base and aminoalcohol ligands were synthesized according to known literature procedures [7,8]. 3-(adamantan-1-yl)-3,4-dihydro-2H-benzo[e] [1,3,2]oxazaborinane (1a) H3B·SMe2 (2.6 mL of a 2 M toluene solution, 5.2 mmol) was added dropwise to a stirred solution of 2- ((adamantan-1-ylamino)methyl)phenol (1.22 g, 4.73 mmol) in toluene (2 mL). Gas evolved upon addition of the borane and a white precipitate formed.…”

Section: Generalmentioning

confidence: 99%

“…The resulting organoboron products are remarkably versatile synthons that can be transformed into diverse families of important compounds (Figure 1). However, difficulties associated with synthesis, cost, handling and storage of hydroboranes have continued to plague their practical use at an industrial scale [2]. As such, there has been a considerable amount of research addressed at synthesizing novel boranes for the hydroboration reaction [3].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Reactivity of Novel Boranes Derived from Bulky Salicylaldimines: The Molecular Structure of a Maltolato Compound

et al. 2015

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Reductive amination of salicylaldehyde or 3,5-di-tert-butylsalicylaldehyde and 1-adamantylamine using NaBH4 gave the corresponding aminoalcohols in high yields. Subsequent addition of one equivalent of H3B·SMe2 to the aminoalcohols, with loss of two equivalents of dihydrogen, resulted in the formation of adamantanyl oxazaborinanes (1a,b). The molecular structure of 1b was studied by a single crystal X-ray diffraction study. Crystals were obtained from a saturated Et2O solution and belong to the triclinic space group Pī with unit cell parameters a = 9.1267(4) Å; b = 11.676(2) Å; c = 12.240(3) Å; α = 66.840(3)°; β = 78.529(3)°; and γ = 67.354(3)°. The molecular structure of the addition product (2a) arising from maltol and 1a was also confirmed by single crystal X-ray diffraction. Crystals were obtained from a saturated 1:2 mixture of toluene/Et2O and belong to the orthorhombic space group Pna2(1) with unit cell parameters a = 18.519(6) Å; b = 17.315(5) Å; and c = 12.680(4) Å. The asymmetric unit contains two molecules that differ slightly in some of the dihedral angles.

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Safe Handling of Boranes at Scale

Cited by 46 publications

References 26 publications

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

Process Development and Scale-Up of a Benzoxazepine-Containing Kinase Inhibitor

Synthesis and Reactivity of Novel Boranes Derived from Bulky Salicylaldimines: The Molecular Structure of a Maltolato Compound

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