4-Methylmorpholine → HCID 86595393, compound

HRID 2211843Notes

Reaction equation

CN1CCOCC1.ClC(OCC(C)C)=O.[C:16]([O:20][C:21]([NH:23][C@H:24]([CH2:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=1[F:38])[CH2:25][C:26]([OH:28])=O)=[O:22])([CH3:19])([CH3:18])[CH3:17].Cl.[F:40][C:41]([F:59])([F:58])[O:42][C:43]1[CH:57]=[CH:56][C:46]([CH2:47][CH:48]2[NH:54][CH2:53][CH2:52][CH2:51][NH:50][C:49]2=[O:55])=[CH:45][CH:44]=1>ClCCl>[C:16]([O:20][C:21]([NH:23][C@H:24]([CH2:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=1[F:38])[CH2:25][C:26]([N:54]1[CH2:53][CH2:52][CH2:51][NH:50][C:49](=[O:55])[C@H:48]1[CH2:47][C:46]1[CH:45]=[CH:44][C:43]([O:42][C:41]([F:58])([F:59])[F:40])=[CH:57][CH:56]=1)=[O:28])=[O:22])([CH3:17])([CH3:18])[CH3:19]

Participants

Conditions

Temperature: -20 °C

Procedure

N-Methylmorpholine (0.072 mL) and isobutyl chloroformate (0.039 mL) were added to a stirred solution of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid (95 mg) in dichloromethane (5 mL) at −20° C. and the resultant mixture was stirred for 30 min. Hexahydro-3-[4-(trifluoromethoxy)benzyl]-2H-1,4-diazepin-2-one hydrochloride obtained in Step D (91 mg) and IV-methylmorpholine (0.036 mL) were added. The reaction mixture was stirred for 30 min at −20° C. and 2 h at ambient temperature and then evaporated. The residue was purified by preparative TLC (silica gel, methanol/saturated aqueous ammonium hydroxide/dichloromethane 4.4:0.1:95.5), and the isomers were subsequently resolved by HPLC (ChiralPAK OD, 7% ethanol/hexane) to provide the slower eluting (R,R)-isomer.

Workup

customevaporated
customThe residue was purified by preparative TLC (silica gel, methanol/saturated aqueous ammonium hydroxide/dichloromethane 4.4:0.1:95.5)
customto provide the
washslower eluting (R,R)-isomer

Sources & evidence

ORD record: ord-fe4bf9fbaa314b5080e4348b37b5c746
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07101871B2

Reaction notes

Loading…