Methanol → (3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid

HRID 391783ノート

反応式

HRID 391783 の反応式
C[O:2][C:3]([C@@H:5]1[CH2:14][C:13]2[CH:12]=[C:11]3[O:15][CH2:16][C@H:17]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]5[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=5)=[CH:21][CH:20]=4)[O:18][C:10]3=[CH:9][C:8]=2[CH2:7][N:6]1[C@H:35]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:36][CH3:37])=[O:4].CO.[Li+].[OH-]>C1COCC1>[Cl:34][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][C:30]=1[Cl:33])[CH2:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([C@H:17]2[CH2:16][O:15][C:11]3=[CH:12][C:13]4[CH2:14][C@@H:5]([C:3]([OH:4])=[O:2])[N:6]([C@H:35]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH2:36][CH3:37])[CH2:7][C:8]=4[CH:9]=[C:10]3[O:18]2)=[CH:24][CH:23]=1

参加物

5

反応物 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 58327581(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl ester

生成物 1

HCID 58327369(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid収率 96.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl ester (872 mg) was dissolved in 24 mL THF and 20 mL MeOH and 591 mg LiOH was added. The flask was flushed with nitrogen and placed under a nitrogen balloon and stirred at 0° C. 12 mL water was then added in portions while stirring, then the reaction stirred at rt 15 h. 119 mg LiOH and 6 mL water were added to the reaction and stirring continued for 2 h. 4 mL water was added and stirring continued for 30 min, then 2 mL water was added. After 1.5 h the pH was adjusted to 7 with 2% w/v aqueous citric acid and the reaction extracted with EtOAc. The organic solution was washed with brine and dried over Na2SO4 and evaporated, to give 820 mg desired compound after drying. LCMS: m/z 605 (M+1).

後処理

  1. customThe flask was flushed with nitrogen
  2. addition12 mL water was then added in portions
  3. stirringwhile stirring
  4. stirringthe reaction stirred at rt 15 h
  5. addition119 mg LiOH and 6 mL water were added to the reaction
  6. stirringstirring
  7. addition4 mL water was added
  8. stirringstirring
  9. waitcontinued for 30 min
  10. addition2 mL water was added
  11. waitAfter 1.5 h the pH was adjusted to 7 with 2% w/v aqueous citric acid
  12. extractionthe reaction extracted with EtOAc
  13. washThe organic solution was washed with brine
  14. dry with materialdried over Na2SO4
  15. customevaporated

出典と根拠

ORDレコード
ord-825717d9a7a848458de576914888d3e4
出典データセット
uspto-grants-2013_02
特許番号
US08383644B2

反応ノート

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