Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 2-(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-1-[4-(4-chloro-phenyl)-4-hydroxymethyl-piperidin-1-yl]-ethanone

HRID 2104245Notes

Reaction equation

HRID 2104245 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:14][OH:15])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Cl:16][C:17]1[C:18]([C:27]([F:30])([F:29])[F:28])=[N:19][N:20]([CH2:23][C:24](O)=[O:25])[C:21]=1[CH3:22].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>[Cl:16][C:17]1[C:18]([C:27]([F:29])([F:28])[F:30])=[N:19][N:20]([CH2:23][C:24]([N:11]2[CH2:12][CH2:13][C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)([CH2:14][OH:15])[CH2:9][CH2:10]2)=[O:25])[C:21]=1[CH3:22]

Participants

5

Reactant 3

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1876853(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acidHCID 23136990[4-(4-Chlorophenyl)piperidin-4-yl]methanol

Product 1

HCID 690511062-(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-1-[4-(4-chloro-phenyl)-4-hydroxymethyl-piperidin-1-yl]-ethanone

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

In a 25 mL flask was taken 500 mg of [4-(4-chloro-phenyl)-piperidin-4-yl]-methanol (2.44 mmol, 1.0 equiv), 591 mg of (4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (2.44 mmol, 1.00 equiv), 1.29 g BOP (2.92 mmol, 1.2 equiv), 1.36 mL TEA (9.75 mmol, 4.00 equiv) and 15 mL NMP. A stir bar was placed in the flask and the mixture stirred overnight at room temperature under N2. The crude product was purified by reversed phase HPLC (acetonitrile—H2O with 0.1% TFA as the eluent) to yield 2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-1-[4-(4-chloro-phenyl)-4-hydroxymethyl-piperidin-1-yl]-ethanone. MS (ES) M+H expected=450.0, found=450.3

Workup

  1. customIn a 25 mL flask was taken
  2. customA stir bar was placed in the flask
  3. customThe crude product was purified by reversed phase HPLC (acetonitrile—H2O with 0.1% TFA as the eluent)

Sources & evidence

ORD record
ord-6f21e7334c8f43a186d7d147962bf651
Source dataset
uspto-grants-2009_08
Patent number
US07576218B2

Reaction notes

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