Sodium Hydroxide → (2R*,4S*,5S*,6S*)-N,N-dimethyl-5-(2,5-dimethoxybenzyl)amino-6-diphenylmethyl-1-azabicyclo[2.2.2]octane-2-carboxamide

HRID 862124ノート

反応式

HRID 862124 の反応式
[CH3:1][N:2]([CH3:27])[C:3]([C@H:5]1[CH2:10][C@@H:9]2[CH2:11][CH2:12][N:6]1[C@@H:7]([CH:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:8]2=O)=[O:4].[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:31]=1[CH2:32][NH2:33].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.C(O)(=O)C.O>[CH3:27][N:2]([CH3:1])[C:3]([C@H:5]1[CH2:10][C@@H:9]2[CH2:11][CH2:12][N:6]1[C@@H:7]([CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C@H:8]2[NH:33][CH2:32][C:31]1[CH:34]=[C:35]([O:38][CH3:39])[CH:36]=[CH:37][C:30]=1[O:29][CH3:28])=[O:4]

参加物

10

反応物 4

HCID 14798Sodium HydroxideHCID 186522,5-DimethoxybenzenemethanamineHCID 5049666Sodium triacetoxyborohydrideHCID 70114993(2R*,4S*,6S*)-N,N-dimethyl-5-oxo-6-diphenylmethyl-1-azabicyclo[2,2,2]octane-2-carboxamide

生成物 1

HCID 70114647(2R*,4S*,5S*,6S*)-N,N-dimethyl-5-(2,5-dimethoxybenzyl)amino-6-diphenylmethyl-1-azabicyclo[2.2.2]octane-2-carboxamide収率 70.1%

試薬・触媒・溶媒 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-触媒HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A mixture of compound 34 (2.22 g, 6.13 mmole), 2,5-dimethoxybenzylamine (1.23 g, 7.36 mmole) and CSA (camphersulfonic acid) (20 mg) in toluene (50 ml) was heated at reflux for 24 hours with Dean Stark water separator. The solvent was removed under reduced pressure. The crude imine was used to the next step without purification. A solution of the crude imine in dry THF (20 ml) was added to a solution of NaBH(OAc)3 (3.9 g, 18.4 mmole) and acetic acid (3 ml) in dry THF (20 ml) at 5° C. and stirred at room temperature for 15 hours. The pH value was adjusted to pH=10 by 1N NaOH, and extracted with EtOAc (20 ml×3). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated down. The crude oil was purified by silica gel chromatography (EtOAc:Hexane=1:1 as eluent) to give colorless oil. The oil was purified by recrystallization from MeOH to give compound 35 as colorless crystal (2.21 g, 4.3 mmole, 70%).

後処理

  1. temperaturewas heated
  2. customThe solvent was removed under reduced pressure
  3. customThe crude imine was used to the next step without purification
  4. extractionextracted with EtOAc (20 ml×3)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated down
  8. customThe crude oil was purified by silica gel chromatography (EtOAc:Hexane=1:1 as eluent)
  9. customto give colorless oil
  10. customThe oil was purified by recrystallization from MeOH

出典と根拠

ORDレコード
ord-b7009d613280405ca03aed37cc57ee2e
出典データセット
uspto-grants-1998_02
特許番号
US05716965

反応ノート

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