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

HRID 1798465노트

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HRID 1798465 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][O:23][C:24]3[C:29]([Cl:30])=[CH:28][C:27]([CH3:31])=[CH:26][C:25]=3[Cl:32])=[CH:16][CH:15]=2)[C@@H:10]([C:33]([N:35]([CH2:39][C:40]2[CH:41]=[C:42]([CH:51]=[C:52]([CH2:54][CH2:55][CH2:56][O:57][CH3:58])[CH:53]=2)[O:43][CH2:44][C@@H:45]2[CH2:47][C@H:46]2[C:48]([OH:50])=[O:49])[CH:36]2[CH2:38][CH2:37]2)=[O:34])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:66][C:67]([N:69]([CH3:71])[CH3:70])=[O:68]>CN(C=O)C.CCOCC>[CH:36]1([N:35]([CH2:39][C:40]2[CH:53]=[C:52]([CH2:54][CH2:55][CH2:56][O:57][CH3:58])[CH:51]=[C:42]([O:43][CH2:44][C@@H:45]3[CH2:47][C@H:46]3[C:48]([O:50][CH2:66][C:67]([N:69]([CH3:71])[CH3:70])=[O:68])=[O:49])[CH:41]=2)[C:33]([C@@H:10]2[C@@H:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][O:23][C:24]4[C:29]([Cl:30])=[CH:28][C:27]([CH3:31])=[CH:26][C:25]=4[Cl:32])=[CH:16][CH:15]=3)[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:9]2)=[O:34])[CH2:37][CH2:38]1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 758862-chloro-N,N-dimethylacetamideHCID 68488708(1R,2R)-2-{[3-{[[((3R,4S)-1-(tert-Butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)amino]methyl}-5-(3-methoxypropyl)phenoxy]methyl}cyclopropanecarboxylic Acid

생성물 1

HCID 86641740tert-Butyl (3R,4S)-3-({cyclopropyl[3-[((1R,2R)-2-{[2-(dimethylamino)-2-oxo-ethoxy]carbonyl}cyclopropyl)methoxy]-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
80 °C

실험 절차

To a solution of (1R,2R)-2-{[3-{[[((3R,4S)-1-(tert-butoxycarbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}piperidin-3-yl)carbonyl](cyclopropyl)-amino]methyl}-5-(3-methoxypropyl)phenoxy]methyl}cyclopropanecarboxylic acid (1 eq.) from the previous step in DMF (0.1 M) was added cesium carbonate (2 eq.) and 2-chloro-N,N-dimethylacetamide (1.8 eq.). The reaction was heated to 80° C. for 2 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 was flash column chromatography (SiO2, 90% 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

출처 및 근거

ORD 기록
ord-e171d8ac037e473491ce388f8462cd63
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08343968B2

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