Potassium Carbonate → 3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde

HRID 2427861Notes

Reaction equation

[F:1][CH:2]([F:13])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][C:5]=1[OH:12].C(=O)([O-])[O-].[K+].[K+].Br[CH2:21][CH:22]1[CH2:24][CH2:23]1.[OH-].[Na+]>O1CCCC1>[CH:22]1([CH2:21][O:12][C:5]2[CH:6]=[C:7]([CH:10]=[CH:11][C:4]=2[O:3][CH:2]([F:13])[F:1])[CH:8]=[O:9])[CH2:24][CH2:23]1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 4-difluoromethoxy-3-hydroxybenzaldehyde (10 g, 53 mmol) and potassium carbonate (44 g, 105 mmol) in tetrahydrofuran (100 mL) is cooled to 0° C. and a solution of bromomethylcyclopropane (11 mL, 116.6 mmol) in tetrahydrofuran (50 mL) is added under vigorous stirring. The reaction mixture is heated to reflux under stirring for 7 hours, then fresh bromomethylcyclopropane (5.5 mL, 58.3 mmoles) is added and heating is continued for further 7 hours. The reaction mixture is cooled to room temperature and 2 N sodium hydroxide (100 ml) is added; the aqueous layer is extracted with dichloromethane (2×100 mL), the combined organic layers are dried over Na2SO4 and the solvent is removed under reduced pressure to afford 3-cyclopropylmethoxy-4-difluoromethoxybenzaldehyde (12 g), that is used in the next step without further purification.

Workup

temperatureThe reaction mixture is heated
temperatureto reflux
temperatureheating
waitis continued for further 7 hours
temperatureThe reaction mixture is cooled to room temperature
extractionthe aqueous layer is extracted with dichloromethane (2×100 mL)
dry with materialthe combined organic layers are dried over Na2SO4
customthe solvent is removed under reduced pressure

Sources & evidence

ORD record: ord-437ef0f70c404f518238fa94189af6b2
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07968724B2

Reaction notes

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