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

HRID 1361486

Reaction equation

HRID 1361486 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

This is an example of Procedure B in Scheme 1 above. 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). * It is important to note that during workup, the organic phase should be washed with H2O and saturated NaCl solution, not 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-b5bb72b27b234b83b0b493307b20e09d
Source dataset
uspto-grants-2011_02
Patent number
US07880002B2

Linked notes

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