Citric Acid → (1S,4S)-5-(1-(4-chlorophenyl)cyclopropanecarbonyl)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one

HRID 1697730ノート

反応式

HRID 1697730 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.CS(O)(=O)=O.[C@H:25]12[CH2:31][C@H:28]([NH:29][CH2:30]1)[C:27](=[O:32])[O:26]2.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.CN(C)C=O.C(N(CC)CC)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]([N:29]3[CH2:30][C@@H:25]4[CH2:31][C@H:28]3[C:27](=[O:32])[O:26]4)=[O:13])[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

参加物

9

反応物 4

HCID 311Citric AcidHCID 65578Oxalyl chlorideHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 16086673(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one methanesulfonate

生成物 1

HCID 67277844(1S,4S)-5-(1-(4-chlorophenyl)cyclopropanecarbonyl)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one収率 95%

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 1140Toluene溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒

実験手順

1-(4-chlorophenyl)cyclopropanecarboxylic acid (8.58 g) and dimethylformamide (136 mg) were suspended in toluene (20 mL). The mixture was cooled down to room temperature then a solution of oxalyl chloride (5.25 g) in toluene (6.7 mL) was dropped within 10 min. The reaction mixture was stirred at 0° C. for 30 min and at room temperature for 3 h. At 0-5° C., (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one methanesulfonate (CAS #: 769167-53-5; 8 g) and tetrahydrofuran (13.2 mL) were added to the reaction mixture, followed by a dropwise addition of triethylamine (14.5 g). The mixture was stirred at 22° C. for 16 hr. An aqueous solution of citric acid (10%, 30 mL) was added and the phases were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude mixture was crystallized in a mixture of dichloromethane, ethyl acetate and heptane to yield 10.6 g (95%) of the title compound as a white solid. MS (ESI): m/z=292.07 [M+H]+.

後処理

  1. stirringThe mixture was stirred at 22° C. for 16 hr
  2. customthe phases were separated
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layers were washed with brine (20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude mixture was crystallized in a mixture of dichloromethane, ethyl acetate and heptane

出典と根拠

ORDレコード
ord-25c1674588bc447fa089d81ca5a1c416
出典データセット
uspto-grants-2012_04
特許番号
US08163793B2

反応ノート

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