Hydrochloric Acid → 6-hydroxymethyl-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one

HRID 1176634Notes

Reaction equation

[CH3:1][C:2]1([CH3:17])[C:7](=[O:8])[NH:6][C:5]2[CH:9]=[C:10]([C:13](OC)=[O:14])[CH:11]=[CH:12][C:4]=2[O:3]1.[H-].C([Al+]CC(C)C)C(C)C.Cl>O1CCCC1>[OH:14][CH2:13][C:10]1[CH:11]=[CH:12][C:4]2[O:3][C:2]([CH3:17])([CH3:1])[C:7](=[O:8])[NH:6][C:5]=2[CH:9]=1

Participants

Conditions

Temperature: -40 °C

Procedure

A solution of 75.60 g of methyl 2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylate in 2700 ml of anhydrous tetrahydrofuran is cooled to −40° C. 858 ml of diisobutylaluminium hydride solution (1M in toluene) are added dropwise at −45-−40° C. The reaction mixture is subsequently stirred at −40° C. for a further 2 hours and finally warmed slowly to −20° C. The reaction mixture is poured onto 360 ml of 32% HCl. The phases are separated and the organic phase is washed with 1000 ml of 1M aqueous sodium potassium tartrate solution. The combined aqueous phases are re-extracted with 1000 ml of tetrahydrofuran and the combined organic phases are dried over sodium sulphate and concentrated by evaporation. The residue is taken up in 500 ml of tert-butyl methyl ether and the suspension is stirred at 45° C. over 1 hour. The title compound is obtained as a beige solid by filtration. Rt=2.69.

Workup

temperaturefinally warmed slowly to −20° C
customThe phases are separated
washthe organic phase is washed with 1000 ml of 1M aqueous sodium potassium tartrate solution
extractionThe combined aqueous phases are re-extracted with 1000 ml of tetrahydrofuran
dry with materialthe combined organic phases are dried over sodium sulphate
concentrationconcentrated by evaporation
stirringthe suspension is stirred at 45° C. over 1 hour

Sources & evidence

ORD record: ord-36cadbc771be4d678c0df6667e84f1d9
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07842688B2

Reaction notes

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