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

HRID 2375726Notes

Reaction equation

HRID 2375726 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

4

Reactant 2

HCID 6328Methyl iodide2×HCID 59855121(3S)-3-(4-Hydroxyphenyl)-4-hexynoic acid

Product 1

HCID 59855119(3S)-3-(4-Hydroxy-phenyl)-hex-4-ynoic acid methyl esterYield 123.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

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 hours. An additional portion of methyl iodide (3 mL, 48 mmol) was added, and heating was continued for 24 hours. Potassium salts were removed by filtration and thoroughly rinsed with acetone. The filtrate was concentrated to an oil which was filtered through a 1 cm plug of silica gel. Elution with 2.5% MeOH in DCM followed by concentration provided phenol 1 (21.5 g) 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

  1. temperatureheating
  2. waitwas continued for 24 hours
  3. customPotassium salts were removed by filtration
  4. washthoroughly rinsed with acetone
  5. concentrationThe filtrate was concentrated to an oil which
  6. filtrationwas filtered through a 1 cm plug of silica gel
  7. washElution with 2.5% MeOH in DCM
  8. concentrationfollowed by concentration

Sources & evidence

ORD record
ord-3f246fea1e5f4e3da7c6c771390e33d2
Source dataset
uspto-grants-2008_12
Patent number
US07465804B2

Reaction notes

Loading…