Pyridine → HCID 86696303, compound

HRID 882367Notes

Reaction equation

HRID 882367 reaction equation
[Cl:1][C:2]([O:4][CH:5]([Cl:7])[CH3:6])=[O:3].[NH2:8][CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(Cl)Cl>[ClH:1].[N:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[O:12]1[CH2:13][CH2:14][CH:9]([NH:8][C:2](=[O:3])[O:4][CH:5]([Cl:7])[CH3:6])[CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 4192234-AminotetrahydropyranHCID 5213051-Chloroethyl chloroformate

Product 1

HCID 86696303HCID 86696303, 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, 1.0 mL, 9.27 mmol) was reacted with 4-aminotetrahydropyrane (Oakwood, 899 mg, 0.92 mL, 8.62 mmol) and pyridine (782 mg, 0.8 mL, 9.89 mmol) in methylene chloride (20 mL) at −78° C. for 3 h to give 1-chloroethyl tetrahydro-2H-pyran-4-ylcarbamate compound with pyridine hydrochloride (1:1). A portion of this material (520 mg, 1.61 mmol) in dimethylformamide (5 mL) 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 (151.4 mg, 0.246 mmol) and cesium carbonate (599.5 mg, 1.84 mmol) in dimethylformamide (4.00 mL) at room temperature for 17 h to give 1-(tetrahydro-2H-pyran-4-ylcarbamoyloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate as a white solid (145.7 mg, 75% yield). MS (ES+) m/z calcd. for C39H42Cl2F2N4O7: [(M+H)+]: 787, found: 787

Sources & evidence

ORD record
ord-5a7129a8cab249238dda40601259f494
Source dataset
uspto-grants-2015_03
Patent number
US08993614B2

Reaction notes

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