Hydrochloric Acid → HCID 71737903, compound

HRID 882366Notes

Reaction equation

HRID 882366 reaction equation
CC1(C)[O:6][CH:5]([CH2:7][NH:8][C:9]([O:11][CH:12]([O:14][C:15](=[O:55])[C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23]([C@H:25]3[C@H:29]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=4[F:37])[C@:28]([C:40]4[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][C:41]=4[F:47])([C:38]#[N:39])[C@H:27]([CH2:48][C:49]([CH3:52])([CH3:51])[CH3:50])[NH:26]3)=[O:24])=[C:18]([O:53][CH3:54])[CH:17]=2)[CH3:13])=[O:10])[CH2:4][O:3]1.Cl.CCOCC>C(#N)C>[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][NH:8][C:9]([O:11][CH:12]([O:14][C:15](=[O:55])[C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]([C@H:25]2[C@H:29]([C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=3[F:37])[C@:28]([C:40]3[CH:45]=[CH:44][C:43]([Cl:46])=[CH:42][C:41]=3[F:47])([C:38]#[N:39])[C@H:27]([CH2:48][C:49]([CH3:51])([CH3:50])[CH3:52])[NH:26]2)=[O:24])=[C:18]([O:53][CH3:54])[CH:17]=1)[CH3:13])=[O:10]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86696302HCID 86696302, compound

Product 1

HCID 71737903HCID 71737903, compoundYield 51.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-((2,2-dimethyl-1,3-dioxolan-4-yl)methylcarbamoyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (Example 15, 75.7 mg, 0.092 mmol) in acetonitrile (4 mL) was treated with a 2M solution of hydrochloric acid in ether (Sigma Aldrich, 0.5 mL, 1.00 mmol) and stirred for 70 min. The reaction mixture was concentrated, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate, brine, dried and concentrated. The crude material was then purified by flash chromatography (methylene chloride/methanol) to give 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid 1-(2,3-dihydroxy-propylcarbamoyloxy)-ethyl ester as a white solid (36.6 mg, 50% yield). MS (ES+) m/z calcd. for C37H40Cl2F2N4O8: [(M+H)+]: 777 found: 777

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethyl acetate
  3. washwashed with saturated aqueous sodium bicarbonate, brine
  4. customdried
  5. concentrationconcentrated
  6. customThe crude material was then purified by flash chromatography (methylene chloride/methanol)

Sources & evidence

ORD record
ord-472187f375c54e569b875894d44f8436
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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