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

HRID 1697731Notes

Reaction equation

HRID 1697731 reaction equation
[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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
53 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-14e110729c034d93a22644e65879a026
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

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