Diisopropylethylamine → tert-butyl(3R)-6-cyclohexyl-3-({[(1S)-2-ethoxy-1-(hydroxymethyl)-2-oxoethyl]amino}carbonyl)hexanoate

Temperature

0 °C

A solution of (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid (Preparation 1) (5.00 g, 16.76 mmol) in dichloromethane (75 ml) was treated sequentially with 1-hydroxybenzotriazole hydrate (2.49 g, 18.43 mmol), serine ethyl ester hydrochloride (3.13 g, 18.43 mmol) and N,N-diisopropylethylamine (6.13 ml, 35.19 mmol) and the resulting mixture was stirred at 0° C. under a nitrogen atmosphere for 15 minutes. 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (3.53 g, 18.43 mmol) was then added and the mixture was stirred for 48 hours being allowed to warm to room temperature over this time. The mixture was diluted with dichloromethane (200 ml), washed sequentially with water, aqueous citric acid solution (10% w/v), a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was then purified by column chromatography on silica gel eluting a gradient system of ethyl acetate:pentane (10:90) to (50:50) to afford the title compound as a colourless oil (5.41 g).

1. stirringthe mixture was stirred for 48 hours
2. temperatureto warm to room temperature over this time
3. washwashed sequentially with water, aqueous citric acid solution (10% w/v)
4. dry with materiala saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulphate
5. filtrationfiltered
6. customthe solvent removed under reduced pressure
7. customThe residue was then purified by column chromatography on silica gel eluting a gradient system of ethyl acetate:pentane (10:90) to (50:50)

ORD record

ord-5428313f6ac7474187565f081fde205a

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06448278B2