Trifluoroacetic acid → 5-(2-fluoro-4-(1H-tetrazol-1-yl)phenyl)-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate

HRID 710130Notes

Reaction equation

HRID 710130 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:12]=[N:11][N:10]=[N:9]2)[CH:5]=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]2[O:20][C:19]([CH:21]3[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]3)=[N:18][C:17]=2[CH:34]=1.[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38]>C(Cl)Cl>[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38].[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH:12]=[N:11][N:10]=[N:9]2)[CH:5]=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]2[O:20][C:19]([CH:21]3[CH2:22][CH2:23][NH:24][CH2:25][CH2:26]3)=[N:18][C:17]=2[CH:34]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71114194HCID 71114194, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tert-butyl 4-{5-[2-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-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (150 mg). 5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoroacetate (70 mg, 0.15 mmol) was dissolved in IPA (10 ml), added DiPEA (0.25 ml, 1.2 mmol) and stirred at rt for 30 mins 2-Chloro-5-ethyl piperidine was added to the above reaction mixture and heated the reaction mixture to 90° C. for overnight. After completion of the reaction, work-up (EtOAc/H2O) followed by purification on combiflash using the gradient mixture of ethyl acetate and petether (1:1) as eluent afforded the titled compound (20 mg) as an off-white solid. M.P.: 188-192° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 9.03 (s, 1H), 8.20 (s, 2H), 7.88 (s, 1H), 7.68 (t, J 8.2, 1H), 7.65-7.58 (m, 3H), 7.54-7.49 ((m, 1H), 4.80-4.70 (m, 2H), 3.33-3.23 (m, 1H), 3.22 (t, J 14, 2H), 2.48 (q, J 7.6, 2H), 2.30-2.22 (m, 2H), 2.07-1.95 (m, 2H), 1.20 (t, J 7.6, 3H).

Workup

  1. customDCM removed from the reaction mixture

Sources & evidence

ORD record
ord-550026f6ae234a82bee9f69c57ac8197
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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