Thiomorpholine → 1-(4-Thiomorpholin-4-yl-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

HRID 1400049ノート

反応式

HRID 1400049 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].[NH:27]1[CH2:32][CH2:31][S:30][CH2:29][CH2:28]1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17]([N:27]4[CH2:32][CH2:31][S:30][CH2:29][CH2:28]4)=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 3

HCID 67164ThiomorpholineHCID 23676156Sodium t-butoxideHCID 53432548tert-Butyl 1-(4-bromophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate2 回

生成物 1

HCID 675080811-(4-Thiomorpholin-4-yl-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester収率 31%

試薬・触媒・溶媒 3

HCID 634876Binap, (A+-)-触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

実験手順

To a solution of 1-(4-bromo-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (Intermediate I, 200 mg, 0.59 mmol) in anhydrous toluene (2 mL) were added Pd2(dba)3 (1.3 mg, 0.002 mmol), BINAP (2.8 mg, 0.004 mmol), sodium tert-butoxide (85 mg, 0.89 mmol) and thiomorpholine (0.07 mL, 0.65 mmol) at r.t. and reaction mixture was refluxed for 17 h. Reaction mixture was then concentrated and the crude product was purified by column chromatography (silica gel, 2:8 EtOAc:Pet. ether) to afford the title compound as viscous liquid (66 mg, 31%).

後処理

  1. customreaction mixture
  2. temperaturewas refluxed for 17 h
  3. customReaction mixture
  4. concentrationwas then concentrated
  5. customthe crude product was purified by column chromatography (silica gel, 2:8 EtOAc:Pet. ether)

出典と根拠

ORDレコード
ord-979725f89ae649c893a00e8b3194cfee
出典データセット
uspto-grants-2014_12
特許番号
US08906913B2

反応ノート

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