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

HRID 710120Notes

Reaction equation

HRID 710120 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[CH:14]=[C:13]([S:15]([CH3:18])(=[O:17])=[O:16])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:20]=[CH:21][C:22]2[O:26][C:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[N:24][C:23]=2[CH:33]=1.Cl[C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36].C1(C)C=CC=CC=1>C(Cl)Cl.O>[F:8][C:9]1[CH:14]=[C:13]([S:15]([CH3:18])(=[O:16])=[O:17])[CH:12]=[CH:11][C:10]=1[C:19]1[CH:20]=[CH:21][C:22]2[O:26][C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36])[CH2:29][CH2:28]3)=[N:24][C:23]=2[CH:33]=1

Participants

6

Reactant 3

HCID 1140TolueneHCID 7917Isopropyl chloroformateHCID 710895675-(2-Fluoro-4-(methylsulfonyl)phenyl)-2-(piperidin-4-yl)-benzo[d]oxazole 2,2,2-trifluoroacetate

Product 1

HCID 71114585Isopropyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate (200 mg, 0.42 mmol) dissolved in DCM and added Trifluoroacetic acid (0.75 ml). This mixture was stirred at rt for 2 h. DCM removed from the reaction mixture to obtain 5-(2-fluoro-4-(methylsulfonyl)phenyl)-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (190 mg). 5-(2-fluoro-4-(methylsulfonyl)phenyl)-2-(piperidin-4-yl)-benzo[d]oxazole 2,2,2-trifluoroacetate (190 mg, 0.39 mmol) was dissolved in DCM (20 ml) and added TEA (0.43 ml, 3.12 mmol). This mixture stirred at rt for 30 mins and added isopropyl chloroformate in toluene (0.095 g, 0.78 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 (120 mg) as a pale-yellow solid. M.P.: 96.5-101.2° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 7.87 (s, 1H), 7.81 (dd, J 1.7, 8, 1H), 7.80-7.75 (m, 1H), 7.67 (t, J 7.5, 1H), 7.59 (d, J 8.4, 1H), 7.50 (d, J 8.5, 1H), 4.94 (septet, J 6.2, 1H), 4.19 (d, J 10.9, 2H), 3.22-3.13 (m, 1H), 3.12 (s, 3H), 3.04 (t, J 10.9, 2H), 2.22-2.14 (m, 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-796888eebeb84f64ab41732ea74beedd
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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