Triethylamine → Isopropyl 2-chloro-4-fluoro-5-[(6-methyl-2,3-dihydro-1,4-oxathiine-5-carbonyl)amino]benzoate

HRID 1938840Notes

Reaction equation

S(Cl)(Cl)=O.[CH3:5][C:6]1[O:7][CH2:8][CH2:9][S:10][C:11]=1[C:12]([OH:14])=O.[NH2:15][C:16]1[C:17]([F:29])=[CH:18][C:19]([Cl:28])=[C:20]([CH:27]=1)[C:21]([O:23][CH:24]([CH3:26])[CH3:25])=[O:22].C(N(CC)CC)C>C(Cl)Cl>[Cl:28][C:19]1[CH:18]=[C:17]([F:29])[C:16]([NH:15][C:12]([C:11]2[S:10][CH2:9][CH2:8][O:7][C:6]=2[CH3:5])=[O:14])=[CH:27][C:20]=1[C:21]([O:23][CH:24]([CH3:26])[CH3:25])=[O:22]

Participants

Conditions

Temperature: 35 °C

Procedure

Thionyl chloride (4.2 g, 0.035 mole) was added to a stirring slurry of 5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxylic acid (4.8 g, 0.030 mole) in methylene chloride (40 ml). The mixture was warmed to 35° C. for 3 hours, then left stirring overnight at room temperature. The solution was then evaporated under reduced pressure at about 35° C. The solid residue, crude 5,6-dihydro-2-methyl-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (50 ml) and the solution chilled in ice and treated dropwise with a solution of 1-methylethyl 5-amino-2-chloro-4-fluorobenzoate (7.0 g, 0.030 mole) and triethylamine (3.5 g, 0.035 mole) in methylene chloride (50 ml). The addition was carried out over 2 hours, after which the reaction mixture was stirred at 20°-35° C. for 3 hours.

Workup

waitleft
customThe solution was then evaporated under reduced pressure at about 35° C
dissolutionThe solid residue, crude 5,6-dihydro-2-methyl-1,4-oxathiin-3-carbonyl chloride, was dissolved in methylene chloride (50 ml)
temperaturethe solution chilled in ice
additionThe addition
waitwas carried out over 2 hours
stirringafter which the reaction mixture was stirred at 20°-35° C. for 3 hours

Sources & evidence

ORD record: ord-12e48f01e0774371ade699021cc6a9b1
Source dataset: uspto-grants-1997_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05693827

Reaction notes

Loading…