Acetaldehyde → 1-Ethyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid ethyl ester

HRID 1257568ノート

反応式

HRID 1257568 の反応式
[CH2:1]([O:3][C:4]([C:6]1[CH2:7][N:8]([CH2:15][C:16]2C=CC=CC=2)[CH2:9][C:10]([F:14])([F:13])[C:11]=1[OH:12])=[O:5])[CH3:2].C(=O)C>C(OCC)(=O)C.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[CH2:7][N:8]([CH2:15][CH3:16])[CH2:9][C:10]([F:13])([F:14])[C:11]=1[OH:12])=[O:5])[CH3:2]

参加物

5

反応物 2

HCID 177AcetaldehydeHCID 67343743Ethyl 1-benzyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylate

生成物 1

HCID 673440141-Ethyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid ethyl ester

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 1-benzyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid ethyl ester was (59.46 g, 0.2 mol, prepared according to EP2123651 A1) in ethyl acetate (600 ml) was degassed and charged with acetaldehyde (13.22 g, 0.3 mol) and 10% palladium on activated carbon (6 g). This mixture was allowed to stir for three hours under an atmosphere then filtered through Celite, washed with copious methanol and concentrated under vacuum to give 1-ethyl-5,5-difluoro-4-hydroxy-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid ethyl ester that was immediately taken up into a 3N solution of hydrochloric acid (470 ml) and heated to reflux for four hours. Upon completion, the reaction was cooled to room temperature and concentrated under vacuum to yield 43.5 g 1-ethyl-3,3-difluoro-4,4-dihydroxy-piperidinium as a pale yellow powder (100%) LCMS (Method F): RT=0.13 min, m+H=182.0 1H NMR (400 MHz, DMSO) δ 10.84 (s, 1H), 6.93 (s, 2H), 3.82 (s, 1H), 3.60-3.32 (m, 2H), 3.15 (d, J=41.5, 2H), 3.09 (s, 1H), 2.07 (dd, J=30.7, 17.4, 2H), 1.25 (t, J=7.2, 3H).

後処理

  1. customwas degassed
  2. filtrationthen filtered through Celite
  3. washwashed with copious methanol
  4. concentrationconcentrated under vacuum

出典と根拠

ORDレコード
ord-7b7141ff61b443a2ad4b533f1e815805
出典データセット
uspto-grants-2013_06
特許番号
US08461328B2

反応ノート

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