Trifluoroacetic acid → 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid phosphonooxymethyl ester, trifluoro-acetate salt

HRID 882386Notes

Reaction equation

HRID 882386 reaction equation
C([O:5][P:6]([O:52]C(C)(C)C)([O:8][CH2:9][O:10][C:11](=[O:51])[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([C@H:21]2[C@H:25]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:27]=3[F:33])[C@:24]([C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=3[F:43])([C:34]#[N:35])[C@H:23]([CH2:44][C:45]([CH3:48])([CH3:47])[CH3:46])[NH:22]2)=[O:20])=[C:14]([O:49][CH3:50])[CH:13]=1)=[O:7])(C)(C)C.[F:57][C:58]([F:63])([F:62])[C:59]([OH:61])=[O:60]>ClCCl>[F:57][C:58]([F:63])([F:62])[C:59]([OH:61])=[O:60].[P:6]([O:8][CH2:9][O:10][C:11](=[O:51])[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([C@H:21]2[C@H:25]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:27]=3[F:33])[C@:24]([C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=3[F:43])([C:34]#[N:35])[C@H:23]([CH2:44][C:45]([CH3:46])([CH3:48])[CH3:47])[NH:22]2)=[O:20])=[C:14]([O:49][CH3:50])[CH:13]=1)([OH:52])([OH:7])=[O:5]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 717387574-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid di-tert-butoxy-phosphoryloxymethyl ester

Product 1

HCID 717384274-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid phosphonooxymethyl ester, trifluoro-acetate salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 25 mL pear-shaped flask, (di-tert-butoxyphosphoryloxy)methyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (20 mg, 23.8 μmmol, Example 2) was combined with dichloromethane (1 mL) to give a colorless solution which was cooled in an ice-water bath. After 5 min trifluoroacetic acid (744 mg, 0.5 mL, 6.53 mmol) was added over 8 min. The reaction mixture was concentrated and dried in vacuo overnight to give 4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid phosphonooxymethyl ester, trifluoro-acetate salt, as off-white solids (19.5 mg, 97%).

Workup

  1. customto give a colorless solution which
  2. temperaturewas cooled in an ice-water bath
  3. concentrationThe reaction mixture was concentrated
  4. customdried in vacuo overnight

Sources & evidence

ORD record
ord-d7c320131ac24219bedbf6cc1ee89b01
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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