2,2,2-Trichloroethyl chloroformate → HCID 70002349, compound

HRID 1266704Notes

Reaction equation

HRID 1266704 reaction equation
Cl.C(OC(=O)C(NC1C=CC(C(=N)N)=CC=1)C1C=C(OCC)C(OCCO)=CC=1F)C.[CH2:32]([O:34][C:35](=[O:69])[CH:36]([NH:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]([NH2:68])=[N:59][C:60]([O:62][CH2:63][C:64]([Cl:67])([Cl:66])[Cl:65])=[O:61])=[CH:54][CH:53]=1)[C:37]1[CH:42]=[C:41]([O:43][CH2:44][CH3:45])[C:40]([O:46][CH2:47][CH2:48][OH:49])=[CH:39][C:38]=1[F:50])[CH3:33].ClC(OCC(Cl)(Cl)Cl)=O>>[CH2:32]([O:34][C:35](=[O:69])[C@@H:36]([NH:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]([NH2:68])=[N:59][C:60]([O:62][CH2:63][C:64]([Cl:66])([Cl:67])[Cl:65])=[O:61])=[CH:54][CH:53]=1)[C:37]1[CH:42]=[C:41]([O:43][CH2:44][CH3:45])[C:40]([O:46][CH2:47][CH2:48][OH:49])=[CH:39][C:38]=1[F:50])[CH3:33].[CH2:32]([O:34][C:35](=[O:69])[C@H:36]([NH:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]([NH2:68])=[N:59][C:60]([O:62][CH2:63][C:64]([Cl:66])([Cl:67])[Cl:65])=[O:61])=[CH:54][CH:53]=1)[C:37]1[CH:42]=[C:41]([O:43][CH2:44][CH3:45])[C:40]([O:46][CH2:47][CH2:48][OH:49])=[CH:39][C:38]=1[F:50])[CH3:33]

Participants

5

Reactant 3

HCID 870632,2,2-Trichloroethyl chloroformateHCID 70002338HCID 70002338, compoundHCID 70002371HCID 70002371, compound

Product 2

HCID 70002349HCID 70002349, compoundHCID 70004414HCID 70004414, compound

Procedure

In analogy to example 1.10, the (RS)-(4-carbamimidoyl-phenylamino)-[5-ethoxy-2-fluoro-4-(2-hydroxy-ethoxy)-phenyl]-acetic acid ethyl ester hydrochloride described in example 1.6 was converted to (RS)-{4-[amino-(2,2,2-trichloro-ethoxycarbonylimino)-methyl]-phenylamino}-[5-ethoxy-2-fluoro-4-(2-hydroxy-ethoxy)-phenyl]-acetic acid ethyl ester by a reaction with 2,2,2-trichloroethyl chloroformate. MS: 596 ([M+H]+) This compound was separated into the enantiomers by preparative HPLC on a chiral stationary phase (Chiralpak AD) using heptane/ethanol/diethylamine (60:40:0.2) as a mobile phase to give (S)-{4-[amino-(2,2,2-trichloro-ethoxycarbonylimino)-methyl]-phenylamino}-[5-ethoxy-2-fluoro-4-(2-hydroxy-ethoxy)-phenyl]-acetic acid ethyl ester and (R)-{4-[amino-(2,2,2-trichloro-ethoxycarbonylimino)-methyl]-phenylamino}-[5-ethoxy-2-fluoro-4-(2-hydroxy-ethoxy)-phenyl]-acetic acid ethyl ester. As a by-product, there was obtained (RS)-{4-[amino-(2,2,2-trichloro-ethoxycarbonylimino)-methyl]-phenylamino}-{5-ethoxy-2-fluoro-4-[2-(2,2,2-trichloro-ethoxycarbonyloxy)-ethoxy]-phenyl}-acetic acid ethyl ester. MS: 770.

Workup

  1. customMS: 596 ([M+H]+) This compound was separated into the enantiomers by preparative HPLC on a chiral stationary phase (Chiralpak AD)

Sources & evidence

ORD record
ord-0be7d128ad7546e582622dbeac3efa2d
Source dataset
uspto-grants-2003_04
Patent number
US06548694B2

Reaction notes

Loading…