Sodium borohydride → HCID 67325017, compound

HRID 1397317Notes

Reaction equation

HRID 1397317 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]([C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[C:26]#[N:27])=[N:4][CH2:5][C:6]1([C:12]2[S:13][CH:14]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:16]=2)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.[BH4-].[Na+]>CO.O>[F:32][C:2]([F:1])([F:31])[CH:3]([C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[C:26]#[N:27])[NH:4][CH2:5][C:6]1([C:12]2[S:13][CH:14]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:16]=2)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 86677591HCID 86677591, compound

Product 1

HCID 67325017HCID 67325017, compoundYield 50.4%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

3-(2,2,2-trifluoro-1-(((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)imino)ethyl)benzonitrile (600 mg, 1.3 mmol) was dissolved in MeOH—H2O (20 mL, 8:2 v/v) and cooled to 0° C. Sodium borohydride (250 mg, 6.6 mmol) was added to this solution portionwise. The reaction mixture was allowed to warm up to room temperature, stirred for 2 h, and then quenched with water and concentrated under reduced pressure to remove the MeOH. The aqueous mixture was diluted with EtOAc and the organic layer was washed with H2O and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluant 15-20% EtOAc in petroleum ether) to afford 3-(2,2,2-trifluoro-1-(((4-(4-phenylthiazol-2-yl)tetrahydro-2H-pyran-4-yl)methyl)amino)ethyl)benzonitrile (300 mg, yield 50%). 1H NMR (300 MHz, CDCl3) δ 7.89-7.86 (m, 2H), 7.63-7.60 (dt, J=7.6 Hz, 1.4 Hz, 1H), 7.55-7.51 (m, 2H), 7.50 (s, 1H), 7.47-7.41 (m, 3H), 7.39-7.36 (m, 0.1H), 4.16-4.03 (m, 1H), 3.84-3.74 (m, 2H), 3.71-3.61 (m, 2H), 2.95 (d, J=11.4 Hz, 1H), 2.76 (d, J=11.4 Hz, 1H), 2.36-2.24 (m, 2H), 2.01-1.92 (ddd, J=13.5 Hz, 9.0 Hz, 4.1 Hz, 2H). MS (ESI) m/z: Calculated for C24H22F3N3OS: 457.14. found: 458.2 (M+H)+.

Workup

  1. temperatureto warm up to room temperature
  2. customquenched with water
  3. concentrationconcentrated under reduced pressure
  4. customto remove the MeOH
  5. additionThe aqueous mixture was diluted with EtOAc
  6. washthe organic layer was washed with H2O and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography (silica gel 60-120 mesh, eluant 15-20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-4d9511871f914d9c9a6c4bdec735540d
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

Loading…