Formaldehyde → HCID 86643634, compound

HRID 2061892Notes

Reaction equation

Cl.[I:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([C@H:13]1[CH2:17][CH2:16][NH:15][CH2:14]1)[CH:8]=[C:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:6]2=[O:23].C=O.O.[C:27]([BH3-])#N.[Na+]>CO>[I:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([C@H:13]1[CH2:17][CH2:16][N:15]([CH3:27])[CH2:14]1)[CH:8]=[C:7]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:6]2=[O:23]

Participants

Conditions

Temperature: 23 °C

Procedure

(S)-Ethyl 6-iodo-4-oxo-1-(pyrrolidin-3-yl)-1,4-dihydroquinoline-3-carboxylate hydrochloride (Intermediate 136, 484 mg, 1.08 mmol) was suspended in methanol (15 mL) then 37% formaldehyde in water (405 μl, 5.4 mmol) and sodium cyanoborohydride (612 mg, 9 7 mmol) were added. The reaction was stirred at 23° C. for 16 h. The volume of the reaction was reduced by half and water (25 mL) was added. The suspension was extracted with 2:1 ethyl acetate: tetrahydrofuran (3×, 10 mL). The organic phases were combined, dried over sodium sulfate, and the solvent was removed in vacuo. The residue was passed through a plug of silica gel (2 g) eluting with 10% methanol in dichloromethane to remove any remaining borohydride. The solid was then dried in a vacuum oven at 50° C. for 18 h to give 379 mg (82% yield) of (S)-ethyl 6-iodo-1-(1-methylpyrrolidin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate as an off white solid.

Workup

additionwas added
extractionThe suspension was extracted with 2:1 ethyl acetate
dry with materialdried over sodium sulfate
customthe solvent was removed in vacuo
washeluting with 10% methanol in dichloromethane
customto remove any remaining borohydride
customThe solid was then dried in a vacuum oven at 50° C. for 18 h

Sources & evidence

ORD record: ord-0c55d4bd2a0d401687b69ac00f991844
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08283361B2

Reaction notes

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