Sodium hydride → 4-(6-Methoxy-quinazolin-4-yloxymethyl)-cyclohexanol

HRID 1354221Notes

Reaction equation

[H-].[Na+].[OH:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1.Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1>CN(C=O)C>[CH3:24][O:23][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[N:16]=[CH:15][N:14]=[C:13]2[O:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]1

Participants

Conditions

Temperature: 40 °C

Procedure

Sodium hydride (79 mg (1.5 eq.) was added at 0° C. to a solution of 4-hydroxymethyl-cyclohexanol (3 g, 12 mmol, synthesised analogously to J. Org. Chem. 1994 59 p. 2748–2761) in DMF (30 ml). After 20 minutes, a solution of 4-chloro-6-methoxy-quinazoline (1.94 g, 10 mmol) in DMF (10 ml) was added and the reaction mixture was heated to 40° C. After a further 2 hours, the reaction mixture was concentrated to dryness. The residue was diluted with water (100 ml) and ethyl acetate (100 ml), the phases were separated and the aqueous phase was extracted twice using 50 ml of ethyl acetate each time. The combined organic phases were dried over MgSO4, filtered and concentrated to dryness by rotary evaporation. The residue was purified by column chromatography on silica gel (EtOAc/hexane 1/2).

Workup

customsynthesised analogously to J
waitAfter a further 2 hours
concentrationthe reaction mixture was concentrated to dryness
additionThe residue was diluted with water (100 ml) and ethyl acetate (100 ml)
customthe phases were separated
extractionthe aqueous phase was extracted twice
dry with materialThe combined organic phases were dried over MgSO4
filtrationfiltered
concentrationconcentrated to dryness by rotary evaporation
customThe residue was purified by column chromatography on silica gel (EtOAc/hexane 1/2)

Sources & evidence

ORD record: ord-d6abb23a476e4d798273a21d4882075d
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07223776B2

Reaction notes

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