تفاعل #1155289

معادلة التفاعل

ethanolamine

N-methyl-N-methoxy 2-oxo-3-cyclobutyl propanamide

(R)-Alpine Borane

isobutyraldehyde

→

title compound

N-Methyl-N-methoxy 2-(S)-hydroxy-3-cyclobutyl propanamide

المذيبات

THF

ether

ظروف التفاعل

المعالجة

1. 1
   تركيزwas concentrated
2. 2
   درجة الحرارةThe mixture was cooled to 0° C.
3. 3
   أخرىThe precipitate that formed
4. 4
   ترشيحwas filtered
5. 5
   تركيزthe filtrate was concentrated

الإجراء التجريبي

A mixture of 11.40 g (61.5 mmol) of N-methyl-N-methoxy 2-oxo-3-cyclobutyl propanamide (from Step B) and 250 mL 0.5 N (R)-Alpine Borane® solution in THF was concentrated and stirred at rt for 5 days. The mixture was cooled to 0° C. and quenched with 6.8 mL (75.0 mmol) of isobutyraldehyde. The resulting mixture was diluted with 200 mL of ether and treated with 7.5 mL (125 mmol) of ethanolamine. The precipitate that formed was filtered and the filtrate was concentrated. Flash chromatography on 500 g of silica gel using 9:1 v/v CH2Cl2 as the eluant afforded 11.48 g (99%, 91% ee) of the title compound: 1H NMR (500 MHz) δ 1.59-1.70 (m, 2H), 1.67 (s, 1H), 1.77-1.83 (m, 2H), 1.82-1.92 (m, 1H), 2.03-2.13 (m, 2H), 2.53-2.60 (m, 1H), 3.23 (s, 3H), 3.72 (s, 3H), 4.31 (app d, J=5.5, 1H); HPLC: Chiralpak AS 4.6×250 mm column, 75/25 hexanes/iPrOH, 0.5 mL/min, 210 nm. Retention Times: (S)-Enantiomer, 13.3 min; (R)-enantiomer, 17.2 min.

المصدر