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 861347Notes

Reaction equation

HRID 861347 reaction equation
[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

Participants

6

Reactant 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

Product 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]pyrazineYield 71.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-185d1e683d504761870b6fdf73994f78
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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