Acetic Acid → Biphenyl-2-ylcarbamic Acid

HRID 1897569Notes

Reaction equation

N1CCC([O:7][C:8](=[O:22])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)CC1.ClC1C=C(C=O)C(OC)=CC=1NC(=O)C=C.C(O)(=O)C>CC1CCCO1>[C:11]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:8](=[O:7])[OH:22]

Participants

Conditions

Temperature: 50 °C

Procedure

Biphenyl-2-ylcarbamic acid piperidin-4-yl ester (which may be prepared according to preparation 8 in WO 2004/074246A) (63.0 kg, 212.57 mol) was added to a stirred suspension of N-[2-chloro-4-formyl-5-(methyloxy)phenyl]-2-propenamide (which may be prepared according to Step C (Preparation 1) or C (Preparation 2)) (50.0 kg, 208.62 mol) and acetic acid (12.6 kg, 209.83 mol) in 2-methyltetrahydrofuran (430 kg) at 25° C. The mixture was then heated to 50° C. over 60 mins and held at this temperature for 2 hours. The resulting suspension was cooled to 20° C. over 90 mins and held at this temperature for 4 hours. The suspension was filtered under vacuum and the filter cake was washed with IMS (3×78.9 kg). The solid was dried in a vacuum oven at 50° C. for 10 hours to give biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-formyl-5-methoxyphenyl-carbamoylethyl]piperidin-4-yl ester as a white solid (90.7 kg, 80.6% th).

Workup

temperatureThe resulting suspension was cooled to 20° C. over 90 mins
waitheld at this temperature for 4 hours
filtrationThe suspension was filtered under vacuum
washthe filter cake was washed with IMS (3×78.9 kg)
customThe solid was dried in a vacuum oven at 50° C. for 10 hours

Sources & evidence

ORD record: ord-a9257a691d374c6b91d46c2ea7cf4249
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08519138B2

Reaction notes

Loading…