Toluene → Isopropyl 4-{5-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate

HRID 710134Notes

Reaction equation

HRID 710134 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:10]=[C:11]([C:20]2[CH:21]=[CH:22][C:23]3[O:27][C:26]([CH:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)=[N:25][C:24]=3[CH:34]=2)[CH:12]=[CH:13][C:14]=1[N:15]1[CH:19]=[N:18][N:17]=[N:16]1.Cl[C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37].C1(C)C=CC=CC=1>C(Cl)Cl.O>[F:8][C:9]1[CH:10]=[C:11]([C:20]2[CH:21]=[CH:22][C:23]3[O:27][C:26]([CH:28]4[CH2:29][CH2:30][N:31]([C:36]([O:38][CH:39]([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:33]4)=[N:25][C:24]=3[CH:34]=2)[CH:12]=[CH:13][C:14]=1[N:15]1[CH:19]=[N:18][N:17]=[N:16]1

Participants

6

Reactant 3

HCID 1140TolueneHCID 7917Isopropyl chloroformateHCID 712575575-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate

Product 1

HCID 71114208Isopropyl 4-{5-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-{5-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (120 mg, 0.26 mmol) dissolved in DCM (15 ml) and added Trifluoroacetic acid (0.5 ml). This mixture was stirred at rt for 2 h. DCM removed from the reaction mixture to obtain 5-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (120 mg). 5-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (120 mg, 0.25 mmol) was dissolved in DCM (15 ml) and added TEA (0.27 ml, 2 mmol). This mixture stirred at rt for 30 mins and added isopropyl chloroformate in toluene (61 mg, 0.34 mmol). After 1 h, reaction mass diluted with water and extracted with DCM. Removal of DCM afforded crude. Crude was purified by combiflash using a mixture of EtOAc and Petether (35:65) as eluent to afford the titled compound (20 mg) as an off-white solid. M.P.: 187-191° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.14 (d, J 2.6, 1H), 8.02 (t, J 8.2, 1H), 7.90 (d, J 1.4, 1H), 7.63-7.55 (m, 4H), 4.95 (septet, J 6.2, 1H), 4.20 (d, J 11.2, 2H), 3.22-3.14 (m, 1H), 3.04 (t, J 11.4, 2H), 2.18 (d, J 10.8, 2H), 2.00-1.88 (m, 2H), 1.26 (d, J 6.2, 6H).

Workup

  1. waitAfter 1 h
  2. customreaction mass
  3. extractionextracted with DCM
  4. customRemoval of DCM
  5. customafforded crude
  6. customCrude was purified by combiflash
  7. additiona mixture of EtOAc and Petether (35:65) as eluent

Sources & evidence

ORD record
ord-85ea70e4aff9404080530ca93701f1aa
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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