(+-)-2-Butanol → Sec-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate

HRID 710141Notes

Reaction equation

HRID 710141 reaction equation
FC(F)(F)[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:14]=[C:13]([N:15]2[CH:19]=[N:18][N:17]=[N:16]2)[CH:12]=[CH:11][C:10]=1[C:20]1[CH:21]=[CH:22][C:23]2[O:27][C:26]([CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:25][C:24]=2[CH:34]=1.[CH3:35][CH:36](O)[CH2:37][CH3:38]>CN(C=O)C>[F:8][C:9]1[CH:14]=[C:13]([N:15]2[CH:19]=[N:18][N:17]=[N:16]2)[CH:12]=[CH:11][C:10]=1[C:20]1[CH:21]=[CH:22][C:23]2[O:27][C:26]([CH:28]3[CH2:29][CH2:30][N:31]([C:3]([O:5][CH:36]([CH2:37][CH3:38])[CH3:35])=[O:4])[CH2:32][CH2:33]3)=[N:25][C:24]=2[CH:34]=1

Participants

4

Reactant 2

HCID 6568(+-)-2-ButanolHCID 710900805-(2-fluoro-4-(1H-tetrazol-1-yl)phenyl)-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate

Product 1

HCID 71114199Sec-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylateYield 20.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Tert-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (250 mg, 0.54 mmol) dissolved in DCM (15 ml) and added Trifluoroacetic acid (1 ml). This mixture was stirred at rt for 2 h. DCM removed from the reaction mixture to obtain 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoro acetate (260 mg). 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (150 mg, 0.31 mmol) was dissolved in DMF (2.6 ml) and added N,N-Carbonyl diimidazole (101 mg, 0.63 mmol) and stirred at rt for 1 h. To this mixture added 2-butanol (46 mg, 0.63 mmol) and TEA (0.13 ml, 0.94 mmol) and stirred at 60° C. for overnight. Work up (EtOAc/H2O) and purification of the crude by combiflash with gradient mixture of ethyl acetate and petether (1:1) as eluent afforded the titled compound (30 mg) as an off-white solid. M.P.: 118-122° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.03 (s, 1H), 7.88 (s, 1H), 7.72-7.58 (m, 4H), 7.55-7.50 (m, 1H), 4.82-4.73 (m, 1H), 4.21 (d, J 12.7, 2H), 3.24-3.13 (m, 1H), 3.06 (t, J 11.6, 2H), 2.19 (d, J 10.9, 2H), 2.00-1.88 (m, 2H), 1.69-1.50 (m, 2H), 1.24 (d, J 6.2, 3H), 0.92 (t, J 7.4, 3H).

Workup

  1. stirringstirred at 60° C. for overnight
  2. custom(EtOAc/H2O) and purification of the crude by combiflash
  3. additionwith gradient mixture of ethyl acetate and petether (1:1) as eluent

Sources & evidence

ORD record
ord-c314268b0f3c4ef784e0d6daf5b8fa84
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

Loading…