Sodium Hydroxide → (11R)-11-(chloromethyl)-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amine

HRID 1035538Notes

Reaction equation

S(Cl)([Cl:3])=O.[NH2:5][C:6]1[C:15]2[N:16]=[C:17]3[CH2:22][O:21][CH2:20][C@H:19]([CH2:23]O)[N:18]3[C:14]=2[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1.[OH-].[Na+]>C(#N)C>[Cl:3][CH2:23][C@@H:19]1[N:18]2[C:14]3[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[N:7]=[C:6]([NH2:5])[C:15]=3[N:16]=[C:17]2[CH2:22][O:21][CH2:20]1

Participants

Conditions

Temperature: 70 °C

Procedure

Thionyl chloride (1.5 mL, 20.7 mmol) was added neat to [(11S)-6-amino-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-11-yl]methanol (280 mg, 1.03 mmol). The nearly homogeneous yellow reaction mixture was heated to 70° C. for 2 hours and turned dark red. The reaction mixture was cooled to ambient temperature and poured over ice. While maintaining the temperature at 0° C., the pH of the mixture was brought to 14 by addition of 50% aqueous NaOH. The resulting white suspension was extracted with CHCl3. The layers were separated and the organic layer was dried over Na2SO4 and concentrated under reduced pressure to provide a tan foam. The tan foam was slurried with acetonitrile and filtered to provide 185 mg of the desired product as a white solid, mp 230-232° C.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
additionpoured over ice
temperatureWhile maintaining the temperature at 0° C.
extractionThe resulting white suspension was extracted with CHCl3
customThe layers were separated
dry with materialthe organic layer was dried over Na2SO4
concentrationconcentrated under reduced pressure
customto provide a tan foam
filtrationfiltered

Sources & evidence

ORD record: ord-dc4a7be52e5942819fb1767c3814173f
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546383B2

Reaction notes

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