Sodium borohydride → HCID 71144475, compound

HRID 1396218Notes

Reaction equation

HRID 1396218 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:30])([CH2:24][N:25]1[CH:29]=[N:28][N:27]=[N:26]1)[C:10]([C:13]1[N:18]=[CH:17][C:16](/[CH:19]=[CH:20]\[C:21](=[O:23])[CH3:22])=[CH:15][CH:14]=1)([F:12])[F:11].[BH4-].[Na+]>CO>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:30])([CH2:24][N:25]1[CH:29]=[N:28][N:27]=[N:26]1)[C:10]([C:13]1[N:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[CH:21]([OH:23])[CH3:22])=[CH:15][CH:14]=1)([F:12])[F:11]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 71143714HCID 71143714, compound

Product 1

HCID 71144475HCID 71144475, compoundYield 50.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of (E)-4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)but-3-en-2-one (7; 450 mg, 1.069 mmol) in CH3OH (20 mL) was added NaBH4 (216 mg, 3.20 mmol) at 0° C. under inert atmosphere. The reaction mixture was allowed to warm to RT and maintained for 1 h. After consumption of starting material (monitored by TLC), the reaction mixture was quenched with satd NH4Cl solution (5 mL) and then concentrated under reduced pressure. The residue was diluted with water (10 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with water (25 mL) and brine (25 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography to afford 46 (230 mg, 0.54 mmol, 50%) as a viscous liquid. 1H NMR (500 MHz, CDCl3): δ 8.78 (s, 1H), 8.50 (s, 1H), 7.79 (d, J=8.2 Hz, 1H), 7.52 (d, J=8.2 Hz, 1H), 7.35-7.31 (m, 1H), 6.81-6.74 (m, 1H), 6.68-6.64 (m, 1H), 6.59 (d, J=16.5 Hz, 1H), 6.43 (dd, J=16.5, 5.5 Hz, 1H), 5.60 (d, J=14.5 Hz, 1H), 5.12 (d, J=14.5 Hz, 1H), 4.59-4.56 (m, 1H), 1.76 (br s, OH), 1.40 (d, J=7.0 Hz, 3H). MS (ESI): m/z 424 [M+H]+. HPLC: 98%.

Workup

  1. temperaturemaintained for 1 h
  2. customAfter consumption of starting material (monitored by TLC)
  3. customthe reaction mixture was quenched with satd NH4Cl solution (5 mL)
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with water (10 mL)
  6. extractionextracted with EtOAc (3×25 mL)
  7. washThe combined organic extracts were washed with water (25 mL) and brine (25 mL)
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-daa8ad7a29bd49cf863fc5eb05727c5f
Source dataset
uspto-grants-2014_12
Patent number
US08901121B2

Reaction notes

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