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

Participants

Role	Name	HCID	Charge
Reactant	1-Bromo-3,5-dichloro-2-(2,2-difluoroethoxy)benzene	HCID 44196687	—
Reactant	4'-{(R)-1-[(3-Amino-oxetane-3-carbonyl)-amino]-ethyl}-3-chloro-3'-fluoro-biphenyl-2-carboxylic acid methyl ester	HCID 67979497	—
Reactant	{(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethyl}-carbamic acid tert-butyl ester	HCID 86667254	—
Reactant	(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethylamine	HCID 86667255	—
Reactant	(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	HCID 86667256	—
Product	3-Amino-oxetane-3-carboxylic acid {(R)-1-[3',5'-dichloro-2'-(2,2-difluoro-ethoxy)-3-fluoro-biphenyl-4-yl]-ethyl}-amide	HCID 86667253	—

Reaction Steps

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]+.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08912221B2
Source dataset	uspto-grants-2014_12
ORD ID	ord-1b2a0d412af943c492e1d6600354f016
Source note	uspto-grants-2014_12