Trichloroisocyanuric Acid → (S)-4-(4-oxo-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

HRID 655542ノート

反応式

HRID 655542 の反応式
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][CH2:20][OH:21])[C:13](=[O:22])[C@@H:12]1[CH3:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O>ClCCl.CC1(C)N([O])C(C)(C)CCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][CH:20]=[O:21])[C:13](=[O:22])[C@@H:12]1[CH3:23])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 2

HCID 6909Trichloroisocyanuric AcidHCID 67079818(S)-4-(4-Hydroxy-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

生成物 1

HCID 86638112(S)-4-(4-oxo-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester収率 94%

試薬・触媒・溶媒 2

HCID 2724126Tempo触媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of (S)-4-(4-hydroxy-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (1.67 g, 5.21 mmol) in dichloromethane (18 mL) were added at room temperature trichloroisocyanuric acid (1.28 g, 5.21 mmol) and 2,2,6,6-tetramethylpiperidin-1-oxyl (8 mg, 0.05 mmol), upon which an exothermic reaction (Tmax=36° C.) under gas evolution started. The reaction mixture was stirred for 5 min, then insoluble material was removed by filtration. The filtrate was washed with 1 M aq. sodium thiosulfate solution and brine, dried (MgSO4), filtered, and evaporated to afford (S)-4-(4-oxo-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester (1.56 g). This aldehyde (MS (ISP)=319.1 (M+H)+) was taken up in dichloromethane (9 mL) and added at room temperature to a suspension of (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride (intermediate 2; 853 mg, 5.21 mmol), triethylamine (527 mg, 5.21 mmol), acetic acid (626 mg, 10.4 mmol), and sodium triacetoxyborohydride (1.21 g, 5.73 mmol) in dichloromethane (9 mL). The reaction mixture was stirred for 30 min, then cooled to 0° C. and treated with 25% aq. ammonia solution (1.07 mL), then allowed to reach room temperature and concentrated in vacuo. Chromatography (SiO2; dichloromethane→dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) afforded the title compound (1.26 g, 56%). Colorless gum, MS (ISP)=430.3 (M+H)+.

後処理

  1. customupon which an exothermic reaction (Tmax=36° C.) under gas evolution
  2. custominsoluble material was removed by filtration
  3. washThe filtrate was washed with 1 M aq. sodium thiosulfate solution and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated

出典と根拠

ORDレコード
ord-d0ca63fdbeeb4f9aa75de1029d44da51
出典データセット
uspto-grants-2011_12
特許番号
US08071586B2

反応ノート

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