Pyridine → 1-Chloroethyl morpholine-4-carboxylate

HRID 882360Notes

Reaction equation

HRID 882360 reaction equation
Cl[C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[NH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.N1C=CC=CC=1>C(Cl)Cl>[N:8]1([C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 8083MorpholineHCID 5213051-Chloroethyl chloroformate

Product 1

HCID 143240831-Chloroethyl morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a manner similar to the method described in Example 3, 1-chloroethyl chloroformate (2.64 g, 2 mL, 18.5 mmol) was reacted with morpholine (1.69 g, 1.7 mL, 19.4 mmol) and pyridine (1.68 g, 1.72 mL, 21.2 mmol) in methylene chloride (25 mL) at room temperature overnight to give the crude product, 1-chloroethyl morpholine-4-carboxylate. A portion of 1-chloroethyl morpholine-4-carboxylate (670.1 mg, 3.46 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 (200.5 mg, 0.325 mmol) in the presence of cesium carbonate (1.094 g, 3.36 mmol) in dimethylformamide (7 mL) overnight to give, 1-(4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoyloxy)ethyl morpholine-4-carboxylate as an off-white solid (186.5 mg, 74% yield). MS (ES+) m/z calcd. for C38H41Cl2F2N4O7: [(M+H)+]: 773, found: 773

Sources & evidence

ORD record
ord-b3b226cfb97545daba1361072a594d3c
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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