Ethanolamine → N-Methyl-N-methoxy2-(S)-hydroxy-3-cyclobutyl Propanamide

HRID 2301161노트

반응식

HRID 2301161 반응식
[CH3:1][N:2]([O:12][CH3:13])[C:3](=[O:11])[C:4](=[O:10])[CH2:5][CH:6]1[CH2:9][CH2:8][CH2:7]1.B1([C@H]2[C@H](C)[C@@H]3C(C)(C)[C@H](C3)C2)C2CCCC1CCC2.C(=O)C(C)C.C(CN)O>C1COCC1.CCOCC>[CH3:1][N:2]([O:12][CH3:13])[C:3](=[O:11])[C@@H:4]([OH:10])[CH2:5][CH:6]1[CH2:7][CH2:8][CH2:9]1

참가 물질

7

반응물 4

HCID 700EthanolamineHCID 6561IsobutyraldehydeHCID 18374694N-Methyl-N-methoxy2-oxo-3-cyclobutyl PropanamideHCID 100979710(R)-Alpine borane

생성물 1

HCID 21341076N-Methyl-N-methoxy2-(S)-hydroxy-3-cyclobutyl Propanamide

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  1. concentrationwas concentrated
  2. temperatureThe mixture was cooled to 0° C.
  3. customThe precipitate that formed
  4. filtrationwas filtered
  5. concentrationthe filtrate was concentrated

출처 및 근거

ORD 기록
ord-4878fdd51804435299c45577464d3e20
출처 데이터셋
uspto-grants-2002_12
특허 번호
US06498161B1

반응 노트

불러오는 중…