Sodium triacetoxyborohydride → 2-(2-(4-fluorophenyl)oxazol-4-yl)-2-methyl-N-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)propan-1-amine

HRID 1397363Notes

Reaction equation

HRID 1397363 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]([F:31])([F:30])[C:17]1[O:21][N:20]=[C:19]([C:22]2[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=2)[CH:25]=O)[N:18]=1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[O:40][CH:41]=[C:42]([C:44]([CH3:48])([CH3:47])[CH2:45][NH2:46])[N:43]=2)=[CH:35][CH:34]=1>ClCCCl>[F:32][C:33]1[CH:34]=[CH:35][C:36]([C:39]2[O:40][CH:41]=[C:42]([C:44]([CH3:48])([CH3:47])[CH2:45][NH:46][CH2:25][C:24]3[CH:27]=[CH:28][CH:29]=[C:22]([C:19]4[N:18]=[C:17]([C:16]([F:31])([F:30])[F:15])[O:21][N:20]=4)[CH:23]=3)[N:43]=2)=[CH:37][CH:38]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 185454733-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzaldehydeHCID 673230862-(2-(4-Fluorophenyl)oxazol-4-yl)-2-methylpropan-1-amine

Product 1

HCID 673249692-(2-(4-fluorophenyl)oxazol-4-yl)-2-methyl-N-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)propan-1-amineYield 18%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Sodiumtriacetoxy borohydride (197 mg, 0.9 mmol) was added to a solution of 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzaldehyde (150 mg, 0.62 mmol) and 2-(2-(4-fluorophenyl)oxazol-4-yl)-2-methylpropan-1-amine (150 mg, 0.64 mmol) in dry DCE (2 mL) at 0° C. under nitrogen atmosphere and stirred at room temperature for 8 h (monitored by TLC, petroleum ether/EtOAc 6:4). Reaction mixture was carefully quenched with 10% NaHCO3 solution and the organic product was extracted with EtOAc. The combined extracts were washed with brine, dried over anhydrous Na2SO, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 10-15% EtOAc in petroleum ether) to get 2-(2-(4-fluorophenyl)oxazol-4-yl)-2-methyl-N-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)propan-1-amine (50 mg, yield 18%). 1H NMR (400 MHz, MeOD) δ 8.01 (m, 2H), 7.96-7.92 (m, 3H), 7.67 (s, 1H), 7.54-7.52 (m, 1H), 7.49-7.45 (m, 1H), 7.20-7.15 (m, 1H), 3.82 (s, 2H), 2.76 (s, 2H), 1.32 (s, 6H). MS (ESI) m/z: Calculated for C23H20F4N4O2: 460.15. found: 461.2 (M+H)+.

Workup

  1. customReaction mixture
  2. customwas carefully quenched with 10% NaHCO3 solution
  3. extractionthe organic product was extracted with EtOAc
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over anhydrous Na2SO
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluant 10-15% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-60af69429260443fa230edf7989e9bfc
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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