Acetic Acid → (s)-4-[4-((s)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

HRID 655543노트

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HRID 655543 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][CH:20]=O)[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.Cl.[CH2:25]1[C:27]2([CH2:32][CH2:31][NH:30][CH2:29][C@H:28]2[OH:33])[CH2:26]1.C(N(CC)CC)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].N>ClCCl>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][CH2:20][N:30]2[CH2:31][CH2:32][C:27]3([CH2:25][CH2:26]3)[C@H:28]([OH:33])[CH2:29]2)[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

참가 물질

8

반응물 6

HCID 176Acetic AcidHCID 222AmmoniaHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 44541812(4S)-6-Azaspiro[2.5]octan-4-ol hydrochloride2회HCID 86638112(S)-4-(4-oxo-butyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester

생성물 1

HCID 67080066(s)-4-[4-((s)-4-Hydroxy-6-aza-spiro[2.5]oct-6-yl)-butyl]-2-methyl-3-oxo-piperazine-1-carboxylic acid benzyl ester수율 56%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

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)+.

후처리

  1. customto reach room temperature
  2. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-930ff55adfaa4483bbe2e4d9f9dbed35
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08071586B2

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