Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 1-[2-(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-4-(4-chloro-phenyl)-piperidine-4-carboxylic acid methyl ester

HRID 2104233Notes

Reaction equation

HRID 2104233 reaction equation
Cl.[CH3:2][O:3][C:4]([C:6]1([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5].[Cl:19][C:20]1[C:21]([C:30]([F:33])([F:32])[F:31])=[N:22][N:23]([CH2:26][C:27](O)=[O:28])[C:24]=1[CH3:25].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN1C(=O)CCC1>[CH3:2][O:3][C:4]([C:6]1([C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[CH2:7][CH2:8][N:9]([C:27](=[O:28])[CH2:26][N:23]2[C:24]([CH3:25])=[C:20]([Cl:19])[C:21]([C:30]([F:33])([F:32])[F:31])=[N:22]2)[CH2:10][CH2:11]1)=[O:5]

Participants

5

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1876853(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acidHCID 49760785Methyl 4-(4-chlorophenyl)piperidine-4-carboxylate hydrochloride

Product 1

HCID 161282741-[2-(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-4-(4-chloro-phenyl)-piperidine-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

In a 25 mL flask was added 4-(4-chloro-phenyl)-piperidine-4-carboxylic acid methyl ester hydrochloride (1.87 mmol, 1.0 equiv), 453 mg of (4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (1.87 mmol, 1.00 equiv), 990 mg BOP (2.24 mmol, 1.2 equiv), 1.04 mL TEA (7.46 mmol, 4.00 equiv) and 10 mL NMP. A stir bar was placed in the flask and the reaction mixture was stirred overnight at room temperature under N2 atmosphere. The crude product was purified by normal phase HPLC (EtOAc-hexane as the eluent) to yield 1-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-4-(4-chloro-phenyl)-piperidine-4-carboxylic acid methyl ester: MS (ES) M+H expected=478.1, found=478.3.

Workup

  1. customA stir bar was placed in the flask
  2. customThe crude product was purified by normal phase HPLC (EtOAc-hexane as the eluent)

Sources & evidence

ORD record
ord-b746a46550c44dac978edfce3b2c2803
Source dataset
uspto-grants-2009_08
Patent number
US07576218B2

Reaction notes

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