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

HRID 658265

反応式

HRID 658265 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.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.O[CH2:71][C@@H:72]1[CH2:74][C@H:73]1[C:75]([O:77][CH2:78][CH3:79])=[O:76].C(P(CCCC)CCCC)CCC>C1(C)C=CC=CC=1.CCOC(C)=O.O>[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][CH2:71][C@@H:72]3[CH2:74][C@H:73]3[C:75]([O:77][CH2:78][CH3:79])=[O:76])[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

7

反応物 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 29920784Ethyl (1R,2R)-2-(hydroxymethyl)cyclopropanecarboxylateHCID 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 86639858tert-butyl (3R,4S)-3-({cyclopropyl[3-{[(1R,2R)-2-(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 1140Toluene溶媒HCID 22728543Water ethylacetate溶媒

反応条件

温度
80 °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 toluene (0.1 M) was added 1,1′-(azodicarbonyl)dipiperidine (1.2 eq.), ethyl (1R,2R)-2-(hydroxyl-methyl)cyclopropanecarboxylate (2 eq.) from the previous step, and tri-n-butylphosphine (1.2 eq.). The reaction was heated to 80° C. and stirred for 18 h. While hot, the reaction was diluted with EtOAc/water. The aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 40% EtOAc in Hex) to afford the title compound as an oil.

後処理

  1. extractionThe aqueous layer was extracted with EtOAc
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography (SiO2, 40% EtOAc in Hex)

出典と根拠

ORDレコード
ord-b713bfe33d4947b7845fa1d1652a0f71
出典データセット
uspto-grants-2011_12
特許番号
US08076359B2

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