Hydrochloric Acid → (R)-1-Amino-2-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-propan-2-ol hydrochloride
Reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@@:8]([O:12][Si](C)(C)C)([CH3:11])[C:9]#[N:10])[C:5]([F:17])=[C:4]([Si:18]([CH2:23][CH3:24])([CH2:21][CH3:22])[CH2:19][CH3:20])[CH:3]=1.[ClH:25]>C1COCC1>[ClH:25].[NH2:10][CH2:9][C@:8]([C:6]1[C:5]([F:17])=[C:4]([Si:18]([CH2:21][CH3:22])([CH2:23][CH3:24])[CH2:19][CH3:20])[CH:3]=[C:2]([Br:1])[N:7]=1)([OH:12])[CH3:11]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Borane dimethyl sulfide complex (16.55 g, 218 mmol) was added to a solution of crude (S)-2-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-2-trimethylsilanyloxy-propionitrile (47 g, 109 mmol) in 470 ml THF. The mixture was refluxed for 2 h. The heating bath was removed and the reaction mixture was quenched by careful and dropwise addition of MeOH. After the evolution of gas had ceased, aq. 6M HCl (23.6 ml, 142 mmol) was added slowly. The resulting solution was evaporated and the residue was dissolved in MeOH and evaporated (twice) to yield 44.5 g of a yellow foam, pure enough for further reactions. HPLC: RtH1=2.617 min; ESIMS: 363, 365 [(M+H)+, 1Br]; 1H-NMR (400 MHz, CDCl3): 7.93 (s, br, 3H), 7.53 (d, 1H), 6.11 (s, br, 1H), 3.36-3.27 (m, 1H), 3.18-3.09 (m, 1H), 1.53 (s, 3H), 0.99-0.81 (m, 15H).
Workup
- temperatureThe mixture was refluxed for 2 h
- customThe heating bath was removed
- customthe reaction mixture was quenched by careful and
- additiondropwise addition of MeOH
- customThe resulting solution was evaporated
- dissolutionthe residue was dissolved in MeOH
- customevaporated (twice)
Sources & evidence
- ORD record
- ord-37789f4b3de84173bddf654d7f30389d
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637508B2
Reaction notes
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