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

HRID 1475444
Notes
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Reaction equation

HRID 1475444 reaction equation
CS(OS(C)(=O)=O)(=O)=O.[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23]O)[N:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:13])([CH3:12])[CH3:11].C(N(CC)CC)C.[NH:40]1[CH:44]=[CH:43][CH:42]=[N:41]1>C(Cl)Cl>[C:10]([O:14][C:15]([N:17]1[CH2:22][C@H:21]([CH2:23][N:40]2[CH:44]=[CH:43][CH:42]=[N:41]2)[N:20]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])([CH3:13])([CH3:12])[CH3:11]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 1048PyrazoleHCID 8471TriethylamineHCID 81560Methanesulfonic anhydrideHCID 70980613tert-butyl (2R,5R)-4-benzyl-5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate

Product 1

HCID 70980646(2R,5R)-4-Benzyl-2-methyl-5-pyrazol-1-ylmethyl-piperazine-1-carboxylic acid tert-butyl esterYield 64.8%

Reagents, catalysts & solvents

1
HCID 6344DichloromethaneSolvent2×

Procedure

A solution of methanesulfonic anhydride (0.65 g, 3.72 mmol) in DCM (5 mL) was added slowly to a solution of (2R,5R)-4-benzyl-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (1.08 g, 3.38 mmol) and triethylamine (1.42 mL, 1.02 g, 10.1 mmol) in DCM (10 mL) with stirring under nitrogen and external ice bath cooling. Stirring was continued at 0° C. for 2 h then pyrazole (0.3 g, 4.4 mmol) was added in one portion. Stirring at 20° C. was continued for 18 h, then mixture was partitioned between saturated aqueous NaHCO3 (40 mL) and DCM (3×20 mL). Combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 0-40% Et2O in 40-60 petroleum ether) gave the title compound (0.811 g) as an oil. MS: [M+H]+=371.

Workup

  1. temperatureexternal ice bath cooling
  2. stirringStirring
  3. stirringStirring at 20° C.
  4. waitwas continued for 18 h
  5. custommixture was partitioned between saturated aqueous NaHCO3 (40 mL) and DCM (3×20 mL)
  6. dry with materialCombined organic extracts were dried (Na2SO4)
  7. customevaporated in vacuo
  8. customto give an oil
  9. washChromatography (SiO2; gradient elution with 0-40% Et2O in 40-60 petroleum ether)

Sources & evidence

ORD record
ord-565f4a8c38d94ac8a07d6f5dc35be848
Source dataset
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09018214B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes