Water methylene chloride → Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperazine-1-carboxylate

HRID 710188Notes

Reaction equation

HRID 710188 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]3[O:21][C:20]([C:22]4[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][C:23]=4[F:32])=[N:19][C:18]=3[CH:33]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.C(Cl)Cl.[OH2:37]>C(Cl)Cl>[F:32][C:23]1[CH:24]=[C:25]([S:28]([CH3:31])(=[O:29])=[O:30])[CH:26]=[CH:27][C:22]=1[C:20]1[O:21][C:17]2[CH:16]=[CH:15][C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:1]([O:21][CH:17]([CH3:18])[CH3:16])=[O:37])[CH2:9][CH2:10]3)=[CH:33][C:18]=2[N:19]=1

Participants

4

Reactant 2

HCID 21908982Water methylene chlorideHCID 712570875-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole

Product 1

HCID 71257301Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Intermediate 28 (490 mg, 1.32 mmol), N-Benzylpiprazine (280 mg, 1.6 mmol), K2CO3 (190 mg, 1.4 mmol), CuCl (6.5 mg, 0.05 mmol), acetyl acetone (17 mg, 0.12 mmol) were dissolved in NMP (2 ml). This reaction mixture was stirred at 130° C. for 15 h under N2 atmosphere. Work up (EtOAc/H2O) followed by column purification on 60-120 mesh silica gel using a gradient mixture of EtOAc and Petether (1:1) as eluent afforded 5-(4-benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole (250 mg) as a yellow solid. 5-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole (130 mg, 0.28 mmol) dissolved in DCM (15 ml) and added isopropylchloro formate (102 mg, 0.84 mmol). This mixture was stirred at reflux for 18 h. Work up (DCM/H2O) followed by purification of the crude by column chromatography on 230-400 mesh silica gel using a gradient mixture of EtOAc and Petether (30:70) as eluent afforded the titled compound (25 mg) as a pale-yellow solid. M.P.: 231-234° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.28 (d, J 8.7, 1H), 7.96 (d, J 1.6, 1H), 7.68-7.64 (m, 2H), 7.57-7.47 (m, 2H), 4.95 (septet, J 6.2, 1H), 3.71-3.63 (m, 4H), 3.12-3.06 (m, 4H), 1.26 (d, J 6.2, 6H).

Workup

  1. temperatureat reflux for 18 h
  2. customfollowed by purification of the crude by column chromatography on 230-400 mesh silica gel using
  3. additiona gradient mixture of EtOAc and Petether (30:70) as eluent

Sources & evidence

ORD record
ord-64290fe5798a4e2891ac79da6a3db324
Source dataset
uspto-grants-2015_11
Patent number
US09181214B2

Reaction notes

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