Sodium borohydride → HCID 71143782, compound

HRID 1396216Notes

Reaction equation

HRID 1396216 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:32])([CH2:26][N:27]1[CH:31]=[N:30][N:29]=[N:28]1)[C:10]([C:13]1[N:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[C:21](OCC)=[O:22])=[CH:15][CH:14]=1)([F:12])[F:11].[H-].C([Al+]CC(C)C)C(C)C.[BH4-].[Na+]>C(Cl)Cl.CO>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:32])([CH2:26][N:27]1[CH:31]=[N:30][N:29]=[N:28]1)[C:10]([C:13]1[N:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[CH2:21][OH:22])=[CH:15][CH:14]=1)([F:12])[F:11]

Participants

6

Reactant 3

HCID 4311764Sodium borohydrideHCID 21225700DiisobutylaluminumhydrideHCID 71164844HCID 71164844, compound

Product 1

HCID 71143782HCID 71143782, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (E)-ethyl 3-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl) pyridin-3-yl)acrylate (4; 150 mg, 0.332 mmol) in dry CH2Cl2 (5 mL) was added diisobutylaluminum hydride (DIBAL-H, 1.6 M in toluene; 0.42 mL, 0.66 mmol) at −78° C. and maintained for 2 h under inert atmosphere. After completion of reaction (by TLC), the reaction was quenched with CH3OH (2 mL) and the obtained heterogeneous mixture was then filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure to obtain the residue. The residue was dissolved in CH3OH (4 mL), and the mixture was stirred at 0° C. under inert atmosphere. Sodium borohydride (NaBH4; 18.9 mg, 0.499 mmol) was added to the stirring solution, and the mixture was maintained at the same temperature for 30 min. The reaction mixture was quenched with satd NH4Cl solution (5 mL) and extracted with EtOAc (3×20 mL). The organic extracts were washed with water (20 mL) and brine (20 mL), dried over anhydrous Na2SO4 and then concentrated in vacuo. Purification by silica gel column chromatography (eluting with 65-75% EtOAc/hexanes) yielded 43 (80 mg, 0.19 mmol, 58%). 1H NMR (500 MHz, CDCl3): δ 8.75 (s, 1H), 8.51 (s, 1H), 7.79 (dd, J=8.5, 2.0 Hz, 1H), 7.52 (d, J=8.5 Hz, 1H), 7.36-7.31 (m, 1H), 6.78-6.74 (m, 1H), 6.68 (br s, OH), 6.67-6.63 (m, 2H), 6.54-6.49 (m, 1H), 5.58 (d, J=14.5 Hz, 1H), 5.11 (d, J=14.5 Hz, 1H), 4.41-4.39 (m, 2H), 3.45 (br s, OH). MS (ESI): m/z 410 [M+H]+. HPLC: 99%.

Workup

  1. temperaturemaintained for 2 h under inert atmosphere
  2. customAfter completion of reaction (by TLC)
  3. customthe reaction was quenched with CH3OH (2 mL)
  4. filtrationthe obtained heterogeneous mixture was then filtered through a pad of Celite®
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customto obtain the residue
  7. temperaturethe mixture was maintained at the same temperature for 30 min
  8. customThe reaction mixture was quenched with satd NH4Cl solution (5 mL)
  9. extractionextracted with EtOAc (3×20 mL)
  10. washThe organic extracts were washed with water (20 mL) and brine (20 mL)
  11. dry with materialdried over anhydrous Na2SO4
  12. concentrationconcentrated in vacuo
  13. customPurification
  14. washby silica gel column chromatography (eluting with 65-75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1986f4fc701d4c4e91f6b8f9e53d6384
Source dataset
uspto-grants-2014_12
Patent number
US08901121B2

Reaction notes

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