Pyrazole → (2R,5R)-4-Benzyl-2-methyl-5-pyrazol-1-ylmethyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475406Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14]O)[N:11]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:10][C@H:9]1[CH3:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.[NH:36]1[CH:40]=[CH:39][CH:38]=[N:37]1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][N:36]2[CH:40]=[CH:39][CH:38]=[N:37]2)[N:11]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:10][C@H:9]1[CH3:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 10 °C

Procedure

To a stirred solution of (2R,5R)-4-benzyl-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.96 g, 3 mmol) in DCM (10 mL) externally cooled in an ice-methanol bath was added triethylamine (0.91 g, 1.25 mL, 9 mmol) followed, dropwise over 0.05 h, methylsulfonyl chloride (0.38 g, 0.26 mL, 3.3 mmol). The mixture was stirred at 0-20° C. for 2 h, then pyrazole (0.27 g, 4 mmol) was added in one portion and stirring continued at 20° C. for 7 days. Mixture was poured into saturated aqueous NaHCO3 and extracted with DCM (3×20 mL). Combined organic extracts were dried (Na2SO4) then evaporated in vacuo to give an oil. Chromatography (SiO2, 0-100% Et2O in petrol) gave the title compound (0.24 g). MS: [M+H]+=371.

Workup

stirringstirring
waitcontinued at 20° C. for 7 days
extractionextracted with DCM (3×20 mL)
dry with materialCombined organic extracts were dried (Na2SO4)
customthen evaporated in vacuo
customto give an oil

Sources & evidence

ORD record: ord-5edc8cd296de43e8b3f27705e914123c
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

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