1-(4-Chlorobenzoyl)piperazine → 3-[4-(4-Chloro-benzoyl)-piperazin-1-yl]4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1947072Notes

Reaction equation

HRID 1947072 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[CH:10]([O:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[O:22])=[CH:17][CH:16]=1>CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([OH:11])[CH:12]([N:26]2[CH2:25][CH2:24][N:23]([C:21](=[O:22])[C:18]3[CH:17]=[CH:16][C:15]([Cl:14])=[CH:20][CH:19]=3)[CH2:28][CH2:27]2)[CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 41014841-(4-Chlorobenzoyl)piperazineHCID 10103880tert-Butyl 6-Oxa-3-azabicyclo(3.1.0)hexane-3-carboxylate

Product 1

HCID 669686813-[4-(4-Chloro-benzoyl)-piperazin-1-yl]4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl esterYield 92.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

6-Oxa-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (0.5 g 1 eq) and (4-Chloro-phenyl)-piperazin-1-yl-methanone (0.6 g 1 eq) were dissolved in CH3CN (5 mL). Ca(OTf)2 (0.456 g, 0.5 eq) was added into the mixture. Reaction mixture was stirred at RT for overnight, then 80-85° C. for 8 h. After concentrating and adding EtOAc 20 mL to the residue, the organic phase was washed with H2O, dried over Na2SO4. The resulting oil was purified by column chromatography (EtOAc:MeOH:Et3N 10:1:0.01) to give 1.01 g of desired product as a sticky oil (92% yield). * Note: During workup, the organic phase should be washed with H2O and Sat. NaCl solution. DO NOT was with saturated NaHCO3 solution!

Workup

  1. customReaction mixture
  2. wait80-85° C. for 8 h
  3. concentrationAfter concentrating
  4. additionadding EtOAc 20 mL to the residue
  5. washthe organic phase was washed with H2O
  6. dry with materialdried over Na2SO4
  7. customThe resulting oil was purified by column chromatography (EtOAc:MeOH:Et3N 10:1:0.01)

Sources & evidence

ORD record
ord-4cb9b3b149d74a43b76ddd8b57d63f87
Source dataset
uspto-grants-2013_03
Patent number
US08399455B2

Reaction notes

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