HCID 71738358, compound → HCID 71738359, compound

HRID 882385Notes

Reaction equation

HRID 882385 reaction equation
[P:1]([O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][C:18]([O:20][CH2:21][O:22][C:23](=[O:77])[C:24]1[CH:29]=[C:28](CC2C=CC=CC=2)[C:27]([NH:37][C:38]([C@H:40]2[C@H:44]([C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[C:46]=3[F:52])[C@:43]([C:55]3[CH:60]=[CH:59][C:58]([Cl:61])=[CH:57][C:56]=3[F:62])([C:53]#[N:54])[C@H:42]([CH2:63][C:64]([CH3:67])([CH3:66])[CH3:65])[NH:41]2)=[O:39])=[C:26]([O:68][CH3:69])[C:25]=1CC1C=CC=CC=1)=[O:19])([OH:4])([OH:3])=[O:2].[H][H]>C(OCC)(=O)C.[Pd]>[P:1]([O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][C:18]([O:20][CH2:21][O:22][C:23](=[O:77])[C:24]1[CH:29]=[CH:28][C:27]([NH:37][C:38]([C@H:40]2[C@H:44]([C:45]3[CH:50]=[CH:49][CH:48]=[C:47]([Cl:51])[C:46]=3[F:52])[C@:43]([C:55]3[CH:60]=[CH:59][C:58]([Cl:61])=[CH:57][C:56]=3[F:62])([C:53]#[N:54])[C@H:42]([CH2:63][C:64]([CH3:66])([CH3:67])[CH3:65])[NH:41]2)=[O:39])=[C:26]([O:68][CH3:69])[CH:25]=1)=[O:19])([OH:3])([OH:4])=[O:2]

Participants

5

Reactant 2

HCID 71738358HCID 71738358, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 71738359HCID 71738359, compoundYield 83.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of chiral dibenzyl 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-{2-[2-(2-phosphonooxy-ethoxy)-ethoxy]-ethoxy}-ethoxycarbonyloxymethyl ester (Example 49, 106.7 mg, 0.095 mmol) in ethyl acetate (10 mL) was treated with 10% palladium on carbon (58 mg) under 1 atm of hydrogen for 1 h. The reaction mixture was filtrated and the filtrate was concentrated to give chiral 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-{2-[2-(2-phosphonooxy-ethoxy)ethoxy]-ethoxy}-ethoxycarbonyloxymethyl ester as a white solid (75 mg, 82% yield). MS (ES+) m/z calcd. for C41H49Cl2F2N3O14P: [(M+H)+]: 946, found: 946.

Workup

  1. filtrationThe reaction mixture was filtrated
  2. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-5562980951204d5e9f263a1639e0c1a4
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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