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

HRID 658261ノート

反応式

HRID 658261 の反応式
[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.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:58][C:59]1([CH3:62])[CH2:61][O:60]1>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][CH2:58][C:59]([OH:60])([CH3:62])[CH3:61])[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

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 11208Isobutylene oxide2 回HCID 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

生成物 1

HCID 86639857tert-Butyl (3R,4S)-3-({cyclopropyl[3-(2-hydroxy-2-methylpropoxy)-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
50 °C

実験手順

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 cesium carbonate (2.5 eq.) and 2,2-dimethyloxirane (15 eq.). The reaction was stirred for 18 h at 50° C., then added more 2,2-dimethyloxirane (10 eq.). The reaction was heated to 80° C. and stirred for 4.5 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, 45%→55% EtOAc in Hex) to afford the title compound as an oil.

後処理

  1. temperatureThe reaction was heated to 80° C.
  2. stirringstirred for 4.5 h
  3. temperatureAfter cooling to rt
  4. extractionThe organic extract
  5. washwas washed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (SiO2, 45%→55% EtOAc in Hex)

出典と根拠

ORDレコード
ord-02ac1da583974d39b9acc6b8926e07bb
出典データセット
uspto-grants-2011_12
特許番号
US08076359B2

反応ノート

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