Propylphosphonic anhydride → 4-[2-(4-Chloro-5 methyl-3-trifluoromethyl-pyrazol-1yl)-acetyl]-piperazine-1carboxylic acid tert-butyl ester

HRID 1371992Notes

Reaction equation

[Cl:1][C:2]1[C:3]([C:12]([F:15])([F:14])[F:13])=[N:4][N:5]([CH2:8][C:9]([OH:11])=O)[C:6]=1[CH3:7].[C:16]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C(Cl)Cl>[C:19]([O:18][C:16]([N:23]1[CH2:28][CH2:27][N:26]([C:9](=[O:11])[CH2:8][N:5]2[C:6]([CH3:7])=[C:2]([Cl:1])[C:3]([C:12]([F:15])([F:14])[F:13])=[N:4]2)[CH2:25][CH2:24]1)=[O:17])([CH3:22])([CH3:20])[CH3:21]

Participants

Conditions

Temperature: 0 °C

Procedure

(4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (1.5 g, 6.18 mmol) was taken in dry DCM (20 mL) and cooled to 0° C. To this cold mixture was added N-boc piperazine (1.15 g, 6.18 mmol) followed by addition of T3P (8 g, 12.4 mmol, 50% solution in EtOAc). The reaction was left overnight at rt. The mixture was diluted with CH2Cl2, washed with NaHCO3 soln, brine, dried (Na2SO4) and concentrated to afford the crude product that was washed thoroughly with ether-pet ether to afford 4-[2-(4-Chloro-5 methyl-3-trifluoromethyl-pyrazol-1yl)-acetyl]-piperazine-1carboxylic acid tert-butyl ester (1.2 g, 2.9 mmol). This was dissolved in methanol (25 mL) cooled to 0° C. and HCl saturated ether (3 mL) was added to it. The mixture was stirred at room temperature for 4 h and concentrated. Crystallization from MeOH/Petroleum ether yielded product.

Workup

washwashed with NaHCO3 soln
dry with materialbrine, dried (Na2SO4)
concentrationconcentrated
customto afford the crude product that
washwas washed thoroughly with ether-pet ether

Sources & evidence

ORD record: ord-7c58ef2faee84f9a96e3be8583935d20
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07157464B2

Reaction notes

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