Hydrochloric Acid → 1-(3-Cyclopentyloxy-4-methoxyphenyl)ethanol

HRID 1244877Notes

Reaction equation

[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH:10]=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl-].[NH4+].Cl.[CH:20]1(OC2C=C(C=C(OC)C=2)C=O)CCCC1>C[Mg]Cl.C1COCC1>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:10]([OH:11])[CH3:20])[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 0 °C

Procedure

To the 3-cyclopentyloxy-4-methoxybenzaldehyde in THF solution from Example 1, 3 M methyl magnesium chloride in THF (240 mL) was added dropwise at −10 to -4° C. over 5 hours. After stirring an additional 1 hour at 0° C., HPLC showed 0.07% aldehyde remaining. The reaction mixture was slowly treated with 20% ammonium chloride (340 g) and then acidified with 10% hydrochloric acid (270 g) to a pH of 8. The layers were separated, the aqueous layer extracted with THF, and the combined extracts washed with brine. The organic solution was concentrated to give 1-(3-cyclopentyloxy-4-methoxyphenyl) ethanol as an oil (115.05 g, 81% yield, purity 94.4% by HPLC area). 1H-NMR: 6.93 (d, J=1.8 Hz, 1H), 6.88 (dd, J=8.2 Hz, J=1.8 Hz, 1H), 6.83 (d, J=8.2, 1H), 4.80 (m, 2H), 3.84 (s, 3H), 1.99–1.80 (m, 6H), 1.61 (m, 2H), and 1.48 (d, J=6.4 Hz, 3H). 13C-NMR: 149.2, 147.6, 138.5, 117.5, 112.3, 111.7, 80.3, 70.0, 56.0, 32.7, 25.0, and 24.0.

Workup

customThe layers were separated
extractionthe aqueous layer extracted with THF
washthe combined extracts washed with brine
concentrationThe organic solution was concentrated

Sources & evidence

ORD record: ord-1dae522021904d81962751c1d5a463e6
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07122705B2

Reaction notes

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