Sodium Iodide → ethyl (3S)-3-hydroxy-4-iodobutanoate

Temperature

59 °C

To a solution of ethyl 3(S)-hydroxy-chlorobutyrate (1) (639.0 g, 3.84 mol) in dry acetone (7.7 L) is added anhydrous NaI (2300 g, 15.34 mol). The mixture is stirred vigorously at 58-60° C. for 120 hours under argon atmosphere. The acetone is distilled off under the reduced pressure at 40-60° C. The residue is diluted with water (5.75 L) followed by the addition of saturated Na2S2O3 solution (1.53 L) and t-BuMeO (2.3 L). The mixture is stirred vigorously at ambient temperature for 30 minutes. Then the organic layer is separated and the water phase is extracted additionally with t-BuMeO (2×1.15 L). The combined organic layers are washed with water (800 mL) and dried (MgSO4). Evaporation of the solvent under the reduced pressure (20 mbar) at 40° C. affords 949.9 g (96%) of ethyl 3(S)-hydroxy-4-iodobutyrate (2) as yellow oil (GC purity 85.9%). A product with GC purity of 98-99% can be obtained by vacuum distillation (73-89° C. at 0.180-0.330 mbar) of the crude product. 1H NMR (300 MHz, CDCl3): δ 4.17 (q, J=7.2 Hz, 2H), 3.99 (m, 1H), 3.34 (dd, J=10.3 and 5.2 Hz, 1H), 3.28 (dd, J=10.3 and 5.7 Hz, 1H), 3.21 (br s, 1H), 2.67 (dd, J=16.5 and 4.3 Hz, 1H), 2.58 (dd, J=16.5 and 7.9 Hz, 1H), 1.27 (t, J=7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 171.7, 67.4, 61.0, 40.7, 14.1, 12.0.

1. distillationThe acetone is distilled off under the reduced pressure at 40-60° C
2. additionThe residue is diluted with water (5.75 L)
3. additionfollowed by the addition of saturated Na2S2O3 solution (1.53 L) and t-BuMeO (2.3 L)
4. stirringThe mixture is stirred vigorously at ambient temperature for 30 minutes
5. customThen the organic layer is separated
6. extractionthe water phase is extracted additionally with t-BuMeO (2×1.15 L)
7. washThe combined organic layers are washed with water (800 mL)
8. dry with materialdried (MgSO4)
9. customEvaporation of the solvent under the reduced pressure (20 mbar) at 40° C.

ORD record

ord-a546f0d150fa418bb3985314c10376cf

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08269001B2