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

HRID 2301161ノート

反応式

HRID 2301161 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-4878fdd51804435299c45577464d3e20
出典データセット
uspto-grants-2002_12
特許番号
US06498161B1

反応ノート

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