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

HRID 1697731노트

반응식

HRID 1697731 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
53 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-14e110729c034d93a22644e65879a026
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163793B2

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