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

HRID 1257568노트

반응식

HRID 1257568 반응식
[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]

참가 물질

5

반응물 2

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

생성물 1

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

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-7b7141ff61b443a2ad4b533f1e815805
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08461328B2

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