4-Fluorophenol → (7S,8aS)-7-(4-Fluorophenoxy)methyl-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

HRID 861347ノート

反応式

HRID 861347 の反応式
[OH:1][CH2:2][C@@H:3]1[CH2:18][N:6]2[CH2:7][CH2:8][N:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][N:12]=3)[CH2:10][C@@H:5]2[CH2:4]1.[F:19][C:20]1[CH:25]=[CH:24][C:23](O)=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[F:19][C:20]1[CH:25]=[CH:24][C:23]([O:1][CH2:2][C@@H:3]2[CH2:18][N:6]3[CH2:7][CH2:8][N:9]([C:11]4[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][N:12]=4)[CH2:10][C@@H:5]3[CH2:4]2)=[CH:22][CH:21]=1

参加物

6

反応物 4

HCID 97324-FluorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 15886070(7S,8aS)-7-hydroxymethyl-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

生成物 1

HCID 9841886(7S,8aS)-7-(4-Fluorophenoxy)methyl-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine収率 71.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 0.25 g (0.93 mmol) of (7S,8aS)-7-hydroxymethyl-2-(5-chloropyridin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 14), 0.157 g (1.40 mmol) of 4-fluorophenol, 0.29 g (1.12 mmol) of triphenylphosphine and 0.18 mL (1.1 mmol) of diethyl azodicarboxylate (DEAD) in 10 mL of dry THF was stirred at ambient temperature for 16 h. The solvent was evaporated, the residue was dissolved in chloroform and washed with 1M sodium hydroxide. The organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 1:1 hexane:ethyl acetate gave 0.24 g (71%) of the title compound. mp (.HCl) 221°-224° C. HRMS calcd for C19H22ClFN3O (MH+): 362.1435, found: 362.1415.

後処理

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in chloroform
  3. washwashed with 1M sodium hydroxide
  4. dry with materialThe organic phase was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash silica gel chromatography with 1:1 hexane

出典と根拠

ORDレコード
ord-185d1e683d504761870b6fdf73994f78
出典データセット
uspto-grants-1998_02
特許番号
US05714487

反応ノート

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