An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3-epoxypropane, a key intermediate for the synthesis of ranolazine is described.
http://pubs.acs.org/doi/suppl/10.1021/op300056k
Preparation of 1-(2-Methoxyphenoxy)-2,3-epoxypropane 4.
To a stirring solution of 2-methoxy phenol 2 (10 kg, 80.55 mol) and water (40 L) at about 30 °C was added sodium hydroxide (1.61 kg, 40.25 mol) and water (10 L). After stirring for 30−45 min, epichlorohydrin 3 (22.35 kg, 241.62 mol) was added and stirred for 10−12 h at 25−35 °C. Layers were separated, and water (40 L) was added to the organic layer (bottom layer) containing product. Sodium hydroxide solution (3.22 kg, 80.5 mol) and water (10 L) were added at 27 °C and stirred for 5−6 h at 27 °C.
The bottom product layer was separated and washed with sodium hydroxide solution (3.0 kg 75 mol) and water (30 L). Excess epichlorohydrin (3) was recovered by distillation of the product layer at below 90 °C under vacuum (650−700 mmHg) to give 13.65 kg (94%) of title compound with 98.3% purity by HPLC, 0.2% of 2- methoxy phenol 2, 0.1% of epichlorohydrin 3, 0.1% of chlorohydrin 11, 0.3% of dimer 12 and 0.3% of dihydroxy 13.
1 H NMR (400 MHz, CDCl3, δ) 6.8−7.0 (m, 4H), 4.3 (dd, J = 5.6 Hz, 5.4 Hz, 1H), 3.8 (dd, J = 5.6 Hz, 5.3 Hz, 1H), 3.7 (s, 3H), 3.2−3.4 (m, 1H), 2.8 (dd, J = 5.6 Hz, 5.4 Hz, 1H), 2.7 (dd, J = 5.6 Hz, 5.3 Hz, 1H);
IR (KBr, cm−1 ) 2935 (C−H, aliphatic), 1594 and 1509 (CC, aromatic), 1258 and 1231 (C−O−C, aralkyl ether), 1125 and 1025 (C−O−C, epoxide);
MS (m/z) 181 (M+ + H).
Compound Details
| Properties | |
| MWt | 180.2 |
| MF | C10H12O3 |
CAS 2210-74-4
| Glycidyl 2-methoxyphenyl ether | |
| Guaiacol glycidyl ether |
1H NMR PREDICT
13C NMR PREDICT
COSY PREDICT
CREDIT……….http://www.molbase.com/en/synthesis_2210-74-4-moldata-95563.html
DR REDDYS LABORATORIES
An Efficient Synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key Intermediate of β-Adrenoblockers
† Innovation Plaza, IPD, R&D, Dr. Reddy’s Laboratories Ltd., Survey Nos. 42, 45,46, and 54, Bachupally, Qutubullapur – 500073, Andhra Pradesh, India
‡ Institute of Science and Technology, Center for Environmental Science, JNT University, Kukatpally, Hyderabad – 500 072, Andhra Pradesh, India
Org. Process Res. Dev., 2012, 16 (10), pp 1660–1664
DOI: 10.1021/op300056k
Publication Date (Web): September 14, 2012
Copyright © 2012 American Chemical Society
*Telephone: +91 4044346000. Fax: +91 4044346285. E-mail: rakeshwarb@drreddys.com.
////////////////1-(2-Methoxyphenoxy)-2,3-epoxypropane, β-Adrenoblockers, ranolazine
COc2ccccc2OCC1CO1
OTHER COMPD
Filed under: Uncategorized Tagged: 1-(2-Methoxyphenoxy)-2, 3-epoxypropane, β-Adrenoblockers, Ranolazine
