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 1594573ノート

反応式

HRID 1594573 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 hours. 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 calc'd 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-0008ac6c5cd44833a6832e748989a39d
出典データセット
uspto-grants-2001_09
特許番号
US06284757B1

反応ノート

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