Cesium carbonate → tert-Butyl (3R,4S)-3-({cyclopropyl[3-[2-(cyclopropyloxy)ethoxy]-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)-ethoxy]phenyl}piperidine-1-carboxylate

HRID 658258노트

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HRID 658258 반응식
[CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([OH:51])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:15][CH:14]=3)[CH2:11][CH2:10][N:9]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.Cl[CH2:53][CH2:54][O:55][CH:56]1[CH2:58][CH2:57]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOCC>[CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([O:51][CH2:53][CH2:54][O:55][CH:56]3[CH2:58][CH2:57]3)[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:17][CH:18]=3)[CH2:11][CH2:10][N:9]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 45789860(2-Chloroethoxy)cyclopropaneHCID 68492454tert-Butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]-amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidine-1-carboxylate

생성물 1

HCID 86639856tert-Butyl (3R,4S)-3-({cyclopropyl[3-[2-(cyclopropyloxy)ethoxy]-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)-ethoxy]phenyl}piperidine-1-carboxylate

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxy-propyl)benzyl]-amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}piperidine-1-carboxylate (1 eq.) from Example 1/Step 2 in DMF (0.1 M) was added (2-chloroethoxy)cyclopropane (3 eq.) and cesium carbonate (2 eq.). The reaction was heated to 100° C. and stirred for 3 h. After cooling to rt, the reaction was diluted with ether. The organic extract was washed with water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex) to afford the title compound as an oil.

후처리

  1. temperatureAfter cooling to rt
  2. extractionThe organic extract
  3. washwas washed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex)

출처 및 근거

ORD 기록
ord-28bff665464a425c81a59758e8085d8b
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08076359B2

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