1-Bromo-3,5-dichloro-2-(2,2-difluoroethoxy)benzene → 3-Amino-oxetane-3-carboxylic acid {(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethyl}-amide

HRID 1404549Notes

Reaction equation

HRID 1404549 reaction equation
COC(C1C(C2C=CC([C@H](NC(C3(N)COC3)=O)C)=C(F)C=2)=CC=CC=1Cl)=O.C(OC(=O)N[C@@H](C1C=CC(C2C=C(Cl)C=C(Cl)C=2OCC(F)F)=CC=1F)C)(C)(C)C.BrC1C=C(Cl)C=C(Cl)C=1OCC(F)F.ClC1C(OCC(F)F)=C(C2C=CC([C@H](N)C)=C(F)C=2)C=C(Cl)C=1.C1C2C(COC(=O)[NH:112][C:113]3([C:117](=[O:141])[NH:118][C@@H:119]([C:121]4[CH:126]=[CH:125][C:124]([C:127]5[CH:132]=[C:131]([Cl:133])[CH:130]=[C:129]([Cl:134])[C:128]=5[O:135][CH2:136][CH:137]([F:139])[F:138])=[CH:123][C:122]=4[F:140])[CH3:120])[CH2:116][O:115][CH2:114]3)C3C(=CC=CC=3)C=2C=CC=1>>[Cl:134][C:129]1[C:128]([O:135][CH2:136][CH:137]([F:138])[F:139])=[C:127]([C:124]2[CH:125]=[CH:126][C:121]([C@H:119]([NH:118][C:117]([C:113]3([NH2:112])[CH2:116][O:115][CH2:114]3)=[O:141])[CH3:120])=[C:122]([F:140])[CH:123]=2)[CH:132]=[C:131]([Cl:133])[CH:130]=1

Participants

6

Reactant 5

HCID 441966871-Bromo-3,5-dichloro-2-(2,2-difluoroethoxy)benzene2×HCID 679794974'-{(R)-1-[(3-Amino-oxetane-3-carbonyl)-amino]-ethyl}-3-chloro-3'-fluoro-biphenyl-2-carboxylic acid methyl esterHCID 86667254{(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethyl}-carbamic acid tert-butyl esterHCID 86667255(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethylamineHCID 86667256(3-{(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester

Product 1

HCID 866672533-Amino-oxetane-3-carboxylic acid {(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethyl}-amide

Procedure

The title compound was prepared in analogy to intermediate 4 synthesizing {(R)-1-[3′,5′-dichloro-2′-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethyl}-carbamic acid tert-butyl ester in step A (using 1-bromo-3,5-dichloro-2-(2,2-difluoro-ethoxy)-benzene (intermediate 9) instead of methyl 2-bromo-6-chlorobenzoate), (R)-1-[3′,5′-dichloro-2′-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethylamine in step B and (3-{(R)-1-[3′,5′-dichloro-2′-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester in step C. Colorless oil. MS: 463.1; [M+H]+.

Sources & evidence

ORD record
ord-1b2a0d412af943c492e1d6600354f016
Source dataset
uspto-grants-2014_12
Patent number
US08912221B2

Reaction notes

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