Acetic Anhydride → (S)-N-(3-Chloro-2-hydroxypropyl)acetamide

Triethylamine (10.5 ml, 75.3 mmol, 1.11 eq) is added to a slurry of (S)-1-amino-3-chloro-2-propanol hydrochloride (V, EXAMPLE 1, 9,938 g, 68.059 mmol) in THF (80 ml) at −40° and the mixture stirred for 5 min at −40°. Acetic anhydride (6.78 ml, 71.86 mmol, 1.056 eq) is then added at −40° and the mixture allowed to warm to 20-25° over 1.5 hrs. The precipitate is removed by filtration with reduced pressure and washed with THF. The filtrate is treated with magnesol (5.69 g), which is removed by filtration with reduced pressure and washed with THF (2×60 ml). The filtrate is then concentrated under reduced pressure. The concentrate is purified by flash chromatography (silica gel; eluting with a gradient of 75-100% ethyl acetate/cyclohexane) to give the title compound, NMR (CDCl3) 2.03, 3.32, 3.50-3.57, 3.55, 3.91-4.13, 5.01 and 7.09 δ; CMR (CDCl3) 23.00, 43.31, 46.52, 70.65 and 172.40 δ; MS (CI, NH3), M/Z (relative intensity), 171 (41.6), 169 (100), 154 (22.4), 152 (48.1); [α]25D=−7.44 (c=1.00, H2O).

1. temperatureto warm to 20-25° over 1.5 hrs
2. customThe precipitate is removed by filtration with reduced pressure
3. washwashed with THF
4. additionThe filtrate is treated with magnesol (5.69 g), which
5. customis removed by filtration with reduced pressure
6. washwashed with THF (2×60 ml)
7. concentrationThe filtrate is then concentrated under reduced pressure
8. customThe concentrate is purified by flash chromatography (silica gel
9. washeluting with a gradient of 75-100% ethyl acetate/cyclohexane)

ORDレコード

ord-b0b0dfe9709c4336a444d8a8a7821082

出典データセット

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06613944B2