Pyridine → HCID 86696300, compound

HRID 882363Notes

Reaction equation

HRID 882363 reaction equation
Cl[C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[NH:8]1[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]1.N1C=CC=CC=1>C(Cl)Cl>[Cl:7][CH:5]([O:4][C:2]([N:8]1[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]1)=[O:3])[CH3:6]

Participants

5

Reactant 3

HCID 1049PyridineHCID 5213051-Chloroethyl chloroformateHCID 6484228Thiomorpholine 1,1-dioxide

Product 1

HCID 86696300HCID 86696300, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate (Oakwood, 1.32 g, 1 mL, 9.27 mmol) was reacted with thiomorpholine 1,1-dioxide (1.1638 g, 8.61 mmol) and pyridine (783 mg, 801 μl, 9.9 mmol) in methylene chloride (15 mL) at room temperature for 3 h to give 1,1-dioxo-thiomorpholine-4-carboxylic acid 1-chloro-ethyl ester. A portion of 1,1-dioxo-thiomorpholine-4-carboxylic acid 1-chloro-ethyl ester (577 mg, 1.614 mmol) was then reacted with chiral 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (150.5 mg, 0.244 mmol) in the presence of cesium carbonate (598.4 mg, 1.84 mmol) in dimethylformamide (7 mL) overnight to give 1,1-dioxo-thiomorpholine-4-carboxylic acid 1-(4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoyloxy)-ethyl ester as an off-white solid (175.3 mg, 87% yield). MS (ES+) m/z calcd. for C38H41Cl2F2N4O8S: [(M+H)+]: 821, found: 821

Sources & evidence

ORD record
ord-90fc4538b51d4e6499599ca797e41c7e
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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