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

HRID 241334

反応式

HRID 241334 の反応式
[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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-6ecc576e9acf45318447ef46a70beb11
出典データセット
uspto-grants-2014_02
特許番号
US08648197B2

関連ノート

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