Hydrochloric Acid → (2S,4S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-N-(1-cyanocyclopropyl)-4-hydroxypyrrolidine-2-carboxamide

HRID 1697731ノート

反応式

HRID 1697731 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([N:13]3[CH2:18][C@@H:17]4[CH2:19][C@H:14]3[C:15](=[O:20])[O:16]4)=[O:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.[NH2:22][C:23]1([C:26]#[N:27])[CH2:25][CH2:24]1.C(C(CCCC)C([O-])=O)C.[Na+].Cl.[Cl-].[Na+]>O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]([N:13]3[CH2:18][C@@H:17]([OH:16])[CH2:19][C@H:14]3[C:15]([NH:22][C:23]3([C:26]#[N:27])[CH2:25][CH2:24]3)=[O:20])=[O:12])[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 23672331Sodium 2-ethylhexanoateHCID 67277844(1S,4S)-5-(1-(4-chlorophenyl)cyclopropanecarbonyl)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one

生成物 1

HCID 67278484(2S,4S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-N-(1-cyanocyclopropyl)-4-hydroxypyrrolidine-2-carboxamide収率 88.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
53 °C

実験手順

A mixture of (1S,4S)-5-(1-(4-chlorophenyl)cyclopropanecarbonyl)-2-oxa-5-azabicyclo[2.2.1]heptan-3-one (Example 457a; 10.578 g), 1-aminocyclopropanecarbonitrile hydrochloride (5.94 g), sodium 2-ethylhexanoate (9.44 g) in water (54 mL) was stirred at 52-54° C. for 20 hr. The reaction mixture was diluted with 36 mL tetrahydrofuran. Concentrated hydrochloric acid (1.9 mL) and sodium chloride (18.09 g) were added. The reaction mixture was stirred for 15 min, then extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude mixture was crystallized in a mixture of ethyl acetate and heptane to yield 11.94 g (88%) of the title compound as a white solid. MS (ESI): m/z=374.12 [M+H]+.

後処理

  1. stirringThe reaction mixture was stirred for 15 min
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude mixture was crystallized in a mixture of ethyl acetate and heptane

出典と根拠

ORDレコード
ord-14e110729c034d93a22644e65879a026
出典データセット
uspto-grants-2012_04
特許番号
US08163793B2

反応ノート

読み込み中…