Acetic Acid → HCID 72548393, compound

HRID 2206432Notes

Reaction equation

HRID 2206432 reaction equation
Br.C(O)(=O)C.[Cl:6][C:7]1[C:8]([F:55])=[C:9]([C@@H:13]2[C@:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])([C:18]#[N:19])[C@H:16]([CH2:28][C:29]([CH3:32])([CH3:31])[CH3:30])[NH:15][C@H:14]2[C:33]([NH:35][C:36]2[CH:52]=[CH:51][C:39]([C:40]([O:42][CH2:43][C:44]([O:46]C(C)(C)C)=[O:45])=[O:41])=[CH:38][C:37]=2[O:53][CH3:54])=[O:34])[CH:10]=[CH:11][CH:12]=1>>[C:44]([CH2:43][O:42][C:40](=[O:41])[C:39]1[CH:51]=[CH:52][C:36]([NH:35][C:33]([C@H:14]2[C@H:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([Cl:6])[C:8]=3[F:55])[C@:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])([C:18]#[N:19])[C@H:16]([CH2:28][C:29]([CH3:31])([CH3:32])[CH3:30])[NH:15]2)=[O:34])=[C:37]([O:53][CH3:54])[CH:38]=1)([OH:46])=[O:45]

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 260Hydrogen BromideHCID 867040842-tert-butoxy-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

Product 1

HCID 72548393HCID 72548393, compound

Conditions

Temperature
0 °C

Procedure

In a 25 mL round-bottomed flask, 45% hydrogen bromide in acetic acid (10 mL, 794 μmol) was added. It was cooled down to 0° C., then 2-tert-butoxy-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 (580 mg, 794 μmol) was added as solid. After 30 min, the reaction mixture was concentrated, and water (50 mL) was added to the residue. It was extracted with methylene chloride (2×300 mL). The methylene chloride layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product, which was purified by filtering through a short plug of silica gel 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 carboxymethyl ester as an off white solid (530 mg, 99% yield). LCMS (ES+) m/z calcd. for C33H32Cl2F2N3O6 [(M+H)+]: 674. found: 674.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. additionwater (50 mL) was added to the residue
  3. extractionIt was extracted with methylene chloride (2×300 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product, which
  8. customwas purified
  9. filtrationby filtering through a short plug of silica gel

Sources & evidence

ORD record
ord-cfb1e3c1711b4d14bbd82cdf24e8a297
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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