Ethyl Acetate → 6-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-1,2,3,4-tetrahydro-isoquinoline

HRID 467558ノート

反応式

HRID 467558 の反応式
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH2:18][N:17](S(C2C=CC(C)=CC=2)(=O)=O)[CH2:16][CH2:15]3)[CH2:8]1.COCCO[AlH2-]OCCOC.[Na+].C(OCC)(=O)C.[OH-].[Na+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.O>[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH2:18][NH:17][CH2:16][CH2:15]3)[CH2:8]1

参加物

8

反応物 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 16684438Red-AlHCID 68211015HCID 68211015、化合物

生成物 1

HCID 674693316-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-1,2,3,4-tetrahydro-isoquinoline収率 69.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
60 °C

実験手順

6-((2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl-1′-yl)-2-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline (4.02 g, 9.16 mmol, 1 eq) was dissolved in dry toluene (40.2 mL), degassed with nitrogen and heated to 60° C. Red-Al (11.3 mL, 36.6 mmol, 4 eq) was added slowly and the reaction mixture was heated to 85° C. and stirred overnight. The reaction mixture was cooled to 0° C. and 49 mL of ethyl acetate was added followed slowly by 19.1 mL of a 10M aqueous NaOH solution (190 mmol, 7.6 g NaOH) and 19 mL of water. The reaction mixture was then transferred to a separatory funnel, diluted with brine and extracted with ethyl acetate (2×100 mL). The combined organics were dried over Na2SO4, concentrated under vacuum and purified by column chromatography on silica gel (200 g column; 50 mL/min; 10% MeOH in CH2Cl2 to 5% 7N NH3 in MeOH:90% CH2Cl2), which yielded 1.81 g (69%) of the title compound as a light yellow viscous oil.

後処理

  1. customdegassed with nitrogen
  2. temperaturethe reaction mixture was heated to 85° C.
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. customThe reaction mixture was then transferred to a separatory funnel
  5. extractionextracted with ethyl acetate (2×100 mL)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. custompurified by column chromatography on silica gel (200 g column; 50 mL/min; 10% MeOH in CH2Cl2 to 5% 7N NH3 in MeOH:90% CH2Cl2), which

出典と根拠

ORDレコード
ord-9222bb339ec44b6f90520668a692fe72
出典データセット
uspto-grants-2014_01
特許番号
US08623877B2

反応ノート

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