Water → Rac methyl 4-((2r,3s,4r,5s)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methylbenzoate

HRID 1807246Notes

Reaction equation

HRID 1807246 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.C(Cl)Cl.[NH2:35][C:36]1[CH:45]=[CH:44][C:39]([C:40]([O:42][CH3:43])=[O:41])=[CH:38][C:37]=1[CH3:46].O>C(#N)C>[Cl:1][C:2]1[C:3]([F:31])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:25])[CH3:26])[NH:10][C@H:9]2[C:28]([NH:35][C:36]2[CH:45]=[CH:44][C:39]([C:40]([O:42][CH3:43])=[O:41])=[CH:38][C:37]=2[CH3:46])=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6344Dichloromethane2×HCID 2736799Methyl 4-amino-3-methylbenzoateHCID 59249226(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid2×

Product 1

HCID 59369791Rac methyl 4-((2r,3s,4r,5s)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methylbenzoate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

In a round bottom flask containing (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid (133 mg) was combined with methylene chloride (10 ml), methyl 4-amino-3-methylbenzoate and DiPea. The mixture was stirred at rt for 2 hrs and another 100 mg of (2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxylic acid was added and the mixture was stirred for another 2 hrs. The mixture was pardoned between water (10 ml) and methylene chloride (10 ml) and the organic layer was dried and concentrated to give a solid, which was treated with 3 ml of acetonitrile. The mixture was stirred and filtered. the solid was dried to give a white solid, 102 mg as the desired product. The filtrate was chromatographed on a reverse phase column (40 g, 30-100% acetonitrile) to give another 34 mg of desired product after removal of solvent. combined product: 102+34=136 mg. MS (ES+) m/z Calcd: [(M+H)+]: 614. found: 614.

Workup

  1. stirringthe mixture was stirred for another 2 hrs
  2. customthe organic layer was dried
  3. concentrationconcentrated
  4. customto give a solid, which
  5. stirringThe mixture was stirred
  6. filtrationfiltered
  7. customthe solid was dried

Sources & evidence

ORD record
ord-ed7994cb91ab4630b2eff11380a96589
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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