Hydrochloric Acid → 1-(3-Hydroxymethyl-4-methoxy-phenyl)-cyclopropanecarboxylic acid methyl ester

HRID 1442704Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([CH2:16]Cl)[CH:9]=2)[CH2:7][CH2:6]1)=[O:4].C([O-])([O-])=[O:19].[Na+].[Na+].Cl>O.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-]>[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([CH2:16][OH:19])[CH:9]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

Conditions

Temperature: 65 °C

Procedure

To a suspension of crude 1-(3-chloromethyl-4-methoxy-phenyl)-cyclopropanecarboxylic acid methyl ester (20.0 g) in water (350 mL) was added Bu4NBr (4.0 g) and Na2CO3 (90.0 g, 0.85 mol) at room temperature. The reaction mixture was heated at 65° C. overnight. The resulting solution was acidified with aq. HCl (2 mol/L) and extracted with EtOAc (200 mL×3). The organic layer was washed with brine, dried over anhydrous Na2SO4 and evaporated under vacuum to give crude product, which was purified by column (Petroleum Ether/EtOAc 15:1) to give 1-(3-hydroxymethyl-4-methoxy-phenyl)-cyclopropanecarboxylic acid methyl ester (8.0 g, 39%). 1H NMR (CDCl3, 400 MHz) δ 7.23-7.26 (m, 2H), 6.83 (d, J=8.0 Hz, 1H), 4.67 (s, 2H), 3.86 (s, 3H), 3.62 (s, 3H), 1.58 (q, J=3.6 Hz, 2H), 1.14-1.17 (m, 2H).

Workup

extractionextracted with EtOAc (200 mL×3)
washThe organic layer was washed with brine
dry with materialdried over anhydrous Na2SO4
customevaporated under vacuum
customto give crude product, which
customwas purified by column (Petroleum Ether/EtOAc 15:1)

Sources & evidence

ORD record: ord-60af17ac07e04e0e9e12aea35c27bf75
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07659268B2

Reaction notes

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