Methyl iodide → (3S)-3-(4-Hydroxy-phenyl)-hex-4-ynoic acid methyl ester

HRID 1160271Notes

Reaction equation

[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:13]#[C:14][CH3:15])[CH2:9][C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.[CH3:16]I>CC(C)=O>[CH3:16][O:11][C:10](=[O:12])[CH2:9][C@@H:8]([C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=1)[C:13]#[C:14][CH3:15]

Participants

Conditions

Temperature: 40 °C

Procedure

Phenol 1.4 (23.5 g, 115 mmol) was dissolved in acetone (230 mL) and treated with KHCO3 (11.5 g, 115 mmol). After 15 minutes, methyl iodide (5 mL, 80 mmol) was added, and the reaction stirred at 40° C. for 14 h. An additional portion of methyl iodide (3 mL, 48 mmol) was added and heating was continued for 24 h. Potassium salts were removed by filtration and thoroughly rinsed with acetone. The filtrate was concentrated to an oil which was purified by filtration through a 1 cm plug of silica gel. Elution with 2.5% MeOH in dichloromethane followed by concentration provided phenol 1 (21.5 g, 85%) as a light yellow oil. 1H NMR(500 MHz)(acetone-d6) δ 8.2 (br s, 1H); 7.20 (d, 2H, J=9.5 Hz); 6.77 (d, 2H, J=9.0 Hz); 3.98 (m, 1H); 3.60 (s, 3H); 2.65 (m, 2H); 1.78 (d, 3H, J=2.5 Hz). MS ESI (pos.) m/e: 219.1 (M+H); 241.1 (M+Na).

Workup

temperatureheating
waitwas continued for 24 h
customPotassium salts were removed by filtration
washthoroughly rinsed with acetone
concentrationThe filtrate was concentrated to an oil which
filtrationwas purified by filtration through a 1 cm plug of silica gel
washElution with 2.5% MeOH in dichloromethane
concentrationfollowed by concentration

Sources & evidence

ORD record: ord-3d0ebaaa476b4389a03575300dc2ece0
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07816367B2

Reaction notes

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