Carbamate → [(3S,4R)-4-(4-Chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587408Notes

Reaction equation

HRID 587408 reaction equation
C([O:5][C:6](=[O:29])[N:7]([C@H:9]1[C@H:13]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([F:21])[CH:15]=2)[CH2:12][N:11](CC2C=CC=CC=2)[CH2:10]1)[CH3:8])(C)(C)C.C(=O)([O-])N.FC1C(OC(=O)N([C@H]2[C@H](C3C=CC(Cl)=C(Cl)C=3)CN(C(C3CCN(C(C4(C)CC4)=O)CC3)=O)C2)C)=CC=CN=1.[F:73][C:74]1[CH:79]=[CH:78][C:77](O)=[CH:76][CH:75]=1.C(OC(=O)N([C@@H]1[C@@H](C2C=CC(Cl)=C(Cl)C=2)CNC1)C)(C)(C)C>>[F:73][C:74]1[CH:79]=[CH:78][C:77]([O:5][C:6](=[O:29])[N:7]([C@H:9]2[C@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([F:21])[CH:15]=3)[CH2:12][NH:11][CH2:10]2)[CH3:8])=[CH:76][CH:75]=1

Participants

6

Reactant 5

HCID 276CarbamateHCID 97324-FluorophenolHCID 53244726{(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid 2-fluoro-pyridin-3-yl esterHCID 58009331Rel-tert-butyl ((3R,4S)-4-(3,4-dichlorophenyl)pyrrolidin-3-yl)(methyl)carbamateHCID 58303101[(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid tert-butyl ester

Product 1

HCID 58303096[(3S,4R)-4-(4-Chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

Procedure

After acidic cleavage of the Boc-protecting group from [(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid tert-butyl ester the intermediately built carbamate was prepared in analogy to the procedure described for the synthesis of {(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293, c) with 4-fluorophenol. In analogy to the procedure described for the synthesis of rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid tert-butyl ester (example 1, e) the title compound was prepared from the intermediately built [(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester through cleavage of the benzyl group. MS m/e: 367.0 [M+H]+.

Workup

  1. customwas prepared in analogy to the procedure

Sources & evidence

ORD record
ord-0cb4bbfd635b4d36907c612f05588200
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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