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 1798465ノート

反応式

HRID 1798465 の反応式
[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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e171d8ac037e473491ce388f8462cd63
出典データセット
uspto-grants-2013_01
特許番号
US08343968B2

反応ノート

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