Methanol → HCID 72548159, compound

HRID 2206430Notes

Reaction equation

HRID 2206430 reaction equation
CC1(C)[O:6][CH:5]([CH2:7][NH:8][C:9]([CH2:11][O:12][C:13](=[O:53])[C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([C@H:23]3[C@H:27]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=4[F:35])[C@:26]([C:38]4[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:39]=4[F:45])([C:36]#[N:37])[C@H:25]([CH2:46][C:47]([CH3:50])([CH3:49])[CH3:48])[NH:24]3)=[O:22])=[C:16]([O:51][CH3:52])[CH:15]=2)=[O:10])[CH2:4][O:3]1.CO.FC(F)(F)C(O)=O>O.C(Cl)Cl>[OH:6][CH:5]([CH2:4][OH:3])[CH2:7][NH:8][C:9]([CH2:11][O:12][C:13](=[O:53])[C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([C@H:23]2[C@H:27]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=3[F:35])[C@:26]([C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:39]=3[F:45])([C:36]#[N:37])[C@H:25]([CH2:46][C:47]([CH3:50])([CH3:49])[CH3:48])[NH:24]2)=[O:22])=[C:16]([O:51][CH3:52])[CH:15]=1)=[O:10]

Participants

6

Reactant 3

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 72548158HCID 72548158, compound

Product 1

HCID 72548159HCID 72548159, compoundYield 36.2%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6344DichloromethaneSolvent

Procedure

In a 4 dram vial, 2-((2,2-dimethyl-1,3-dioxolan-4-yl)methylamino)-2-oxoethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (Example 67, 67 mg, 85.1 μmol) was combined with methanol (1 mL), methylene chloride (0.5 mL) and water (2 drops) to give a colorless solution. Trifluoroacetic acid (19.4 mg, 13.1 μL, 170 μmol) was added. The reaction mixture was stirred at room temperature for 5 h then concentrated. The residue was reconstituted with methylene chloride (100 mL). It was washed with saturated aqueous sodium carbonate solution, then brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude residuw was purified by flash chromatography (23 g SUPELCO spherical silica gel column, eluted with methanol in ethyl acetate) 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 (2,3-dihydroxy-propylcarbamoyl)-methyl ester (23 mg, 36% yield). LCMS (ES+) m/z calcd. for C36H39Cl2F2N4O7 [(M+H)+]: 747. found: 747.

Workup

  1. customto give a colorless solution
  2. concentrationthen concentrated
  3. washIt was washed with saturated aqueous sodium carbonate solution
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residuw was purified by flash chromatography (23 g SUPELCO spherical silica gel column, eluted with methanol in ethyl acetate)

Sources & evidence

ORD record
ord-27030faa6dd0466fbcc48f858712272c
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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