Sodium borohydride → tert-butyl((1S)-1-(5-chloro-3-(1-hydroxyethyl)pyridin-2-yl)-2-methylpropyl)carbamate

HRID 1777829Notes

Reaction equation

HRID 1777829 reaction equation
[C:1]([C:4]1[C:5]([C@@H:11]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]([CH3:14])[CH3:13])=[N:6][CH:7]=[C:8]([Cl:10])[CH:9]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>CCO>[C:18]([O:17][C:16](=[O:22])[NH:15][C@H:11]([C:5]1[C:4]([CH:1]([OH:3])[CH3:2])=[CH:9][C:8]([Cl:10])=[CH:7][N:6]=1)[CH:12]([CH3:14])[CH3:13])([CH3:20])([CH3:21])[CH3:19]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 118282595tert-butyl(S)-(1-(3-acetyl-5-chloropyridin-2-yl)-2-methylpropyl)carbamate

Product 1

HCID 118282594tert-butyl((1S)-1-(5-chloro-3-(1-hydroxyethyl)pyridin-2-yl)-2-methylpropyl)carbamateYield 85%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl(S)-(1-(3-acetyl-5-chloropyridin-2-yl)-2-methylpropyl)carbamate (62.3 mg, 191 μmol) in EtOH (1 mL) at 0° C. was added sodium borohydride (7.2 mg, 191 μmol) as a solid. The mixture was stirred at 0° C. for 90 min, then it was quenched with saturated aqueous ammonium chloride (10 mL). The mixture was extracted with EtOAc (20 mL), then the organic phase was washed with brine (10 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluting with 10% EtOAc in hexanes, gradient to 100%) to afford 53.4 mg of tert-butyl((1S)-1-(5-chloro-3-(1-hydroxyethyl)pyridin-2-yl)-2-methylpropyl)carbamate (85% yield). LC-MS tR=1.01 min in 1 min chromatography, MS (ESI) m/z 329.4 [M+H]+. 1H NMR (CDCl3, 400 MHz, mixture of diastereomers): δ 8.44 (d, J=2.4 Hz, 0.3H), 8.41 (d, J=2.4 Hz, 0.7H), 7.86 (d, J=2.4 Hz, 0.7H), 7.77 (d, J=2.4 Hz, 0.3H), 5.44 (d, J=9.6 Hz, 0.7H), 5.31 (m, 0.7H), 5.23 (m, 0.7H), 4.73 (t, J=8.8 Hz, 0.3H), 4.63 (t, J=9.6 Hz, 0.3H), 4.56 (s, 0.3H), 2.18-2.12 (m, 0.3H), 2.08-2.00 (m, 0.7H), 1.56 (d, J=6.8 Hz, 0.9H), 1.52 (d, J=6.8 Hz, 2.1H), 1.40 (s, 9H), 1.11 (d, J=6.8 Hz, 0.9H), 1.00 (d, J=6.8 Hz, 2.1H), 0.80 (d, J=6.8 Hz, 2.1H), 0.69 (d, J=6.8 Hz, 0.9H).

Workup

  1. customit was quenched with saturated aqueous ammonium chloride (10 mL)
  2. extractionThe mixture was extracted with EtOAc (20 mL)
  3. washthe organic phase was washed with brine (10 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (eluting with 10% EtOAc in hexanes, gradient to 100%)

Sources & evidence

ORD record
ord-29cd370797774e51b221faf3e9f5209b
Source dataset
uspto-grants-2016_02
Patent number
US09266886B2

Reaction notes

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