Hydrochloric Acid → Methyl 2-(4-chlorophenyl)-3-hydroxypropanoate

A stirring solution of methyl 2-(4-chlorophenyl)acetate (36.7 g, 199 mmol) (From Example 1, Step 1) and paraformaldehyde (6.27 g, 209 mmol) in DMSO (400 mL) was treated with sodium methoxide (537 mg, 9.94 mmol) at room temperature. The mixture was allowed to stir for two hours to completion and then poured into ice-cold water (700 mL) forming a white emulsion. The quench was neutralized with the addition of 1M HCl solution, and the aqueous was extracted with ethyl acetate (3×). The combined organic portions were washed with water (2×), then brine, dried over MgSO4, and concentrated in vacuo. The residue was filtered through a plug of silica gel eluted stepwise with 9:1 to 1:1 hexanes:ethyl acetate to afford the pure methyl 2-(4-chlorophenyl)-3-hydroxypropanoate (39.4 g, 92%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.32 (d, J=8.4 Hz, 2H), 7.21 (d, J=8.4 Hz, 2H), 4.10 (m, 1H), 3.82 (m, 2H), 3.72 (s, 3H), 2.25 (m, 1H).

1. customforming a white emulsion
2. extractionthe aqueous was extracted with ethyl acetate (3×)
3. washThe combined organic portions were washed with water (2×)
4. dry with materialbrine, dried over MgSO4
5. concentrationconcentrated in vacuo
6. filtrationThe residue was filtered through a plug of silica gel
7. washeluted stepwise with 9:1 to 1:1 hexanes

ORD record

ord-4e04d12403a745d5873f3bf66dd8762b

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853199B2