Methyl 3-Hydroxypropionate

[6149-41-3]  · C4H8O3  · Methyl 3-Hydroxypropionate  · (MW 104.12)

(preparation of a-substituted acrylate and hydracrylate derivatives;1 photochemical conjugate additions;2 protection of the carboxy group3)

Alternate Names: methyl 3-hydroxypropanoate; methyl hydracrylate.

Physical Data: bp 71-73 °C/9 mmHg.4

Analysis of Reagent Purity: 1H NMR and MS.5

Preparative Methods: two methods have been published: reaction of b-Propiolactone with Sodium Methoxide in MeOH (17-36%),5,6 or treatment of 3-hydroxypropionitrile with HCl in aqueous MeOH (68%).4 The latter method appears to be more desirable based upon yield of product and the high cost and toxicity of b-propiolactone.

Preparation of a-Substituted Acrylate and Hydracrylate Derivatives.

Methyl 3-hydroxypropionate (1) is a useful reagent for the preparation of a-substituted acrylate and hydracrylate derivatives. Reaction of the dianion arising from (1) with a variety of electrophiles is shown in eq 1.1 The alkylated products can be dehydrated under acidic (Phosphoric Acid) or basic (p-Toluenesulfonyl Chloride, Pyridine) conditions (eq 2).7 An interesting example of this method is shown in eq 3.8 Treatment of the dianion of (1) with an aldehyde gives an intermediate diol. The less hindered hydroxy group is then eliminated in two steps by reaction with TsCl, followed by treatment with 1,8-Diazabicyclo[5.4.0]undec-7-ene.

Photochemical Conjugate Addition.

A photochemically induced conjugate addition reaction has been observed between (1) and a conjugated enone in the presence of benzophenone (eq 4).2 If the hydroxy group in the product is protected as a THP acetal (3,4-Dihydro-2H-pyran, p-Toluenesulfonic Acid) prior to isolation, the yield increases to 71%.

Protection for the Carboxy Group.

The 2-methoxycarbonylethyl esters derived from (1) have been used as protecting groups for the carboxy functionality.3 Beginning with the carboxylic acid, mixed anhydride formation followed by esterification with (1) in the presence of 4-Dimethylaminopyridine gives the protected ester (eq 5). Deprotection occurs upon treatment with DBU in acetonitrile (eq 6).

Related Reagents.

Ethyl Acrylate; Ethyl 3-Hydroxybutanoate; Methyl 3-(Dimethylamino)propionate; b-Propiolactone.

1. Herrmann, J. L.; Schlessinger, R. H. TL 1973, 2429.
2. Fraser-Reid, B.; Hicks, D. R.; Walker, D. L.; Iley, D. E.; Yunker, M. B.; Tam, S. Y.-K.; Anderson, R. C. TL 1975, 297. Fraser-Reid, B.; Anderson, R. C.; Hicks, D. R.; Walker, D. L. CJC 1977, 55, 3986.
3. Kanda, Y.; Fukuyama, T. JACS 1993, 115, 8451.
4. Ogawa, T.; Nakazato, A.; Sato, M.; Hatayama, K. S 1990, 459.
5. Reeve, C. D.; Crout, D. H. G.; Cooper, K.; Fray, M. J. TA 1992, 3, 785.
6. Bartlett, P. D.; Rylander, P. N. JACS 1951, 73, 4273.
7. Pfeffer, P. E.; Kinsel, E.; Silbert, L. S. JOC 1972, 37, 1256; Grieco, P. A.; Hiroi, K. CC 1972, 1317.
8. Nishitani, K.; Isozaki, M.; Yamakawa, K. CPB 1990, 38, 28.

David L. Clark

University of California, Berkeley, CA, USA

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