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

HRID 1594576Notes

Reaction equation

HRID 1594576 reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:19][N:6]2[CH2:7][CH2:8][N:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=3)[CH2:10][C@@H:5]2[CH2:4]1.[F:20][C:21]1[CH:26]=[CH:25][C:24](O)=[CH:23][CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[F:20][C:21]1[CH:26]=[CH:25][C:24]([O:1][CH2:2][C@@H:3]2[CH2:19][N:6]3[CH2:7][CH2:8][N:9]([C:11]4[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=4)[CH2:10][C@@H:5]3[CH2:4]2)=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 97324-FluorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 57229001(7S,8aS)-7-hydroxymethyl-2-(4-cyanophenyl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 70197806(7S,8aS)-7-(4-Fluorophenoxy)methyl-2-(4-cyanophenyl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.25 g (0.97 mmol) of (7S,8aS)-7-hydroxymethyl-2-(4-cyanophenyl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 16), 0.164 g (1.46 mmol) of 4-fluorophenol, 0.31 g (1.15 mmol) of triphenylphosphine in 10 mL of THF was treated with 0.18 mL (1.15 mmol) of diethyl azodicarboxylate and the solution stirred at ambient temperature for 16 hours. The solvent was removed by rotary evaporation, and the residue partitioned between chloroform and 1M sodium hydroxide. The layers were separated, and the organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 1:1 ethyl acetate:hexane gave 0.225 g (66%) of the title compound. Mp (.HCl) 81-85° C. HRMS calc'd for C21H23FN3O (MH+): 352.1825, found: 352.1817.

Workup

  1. customThe solvent was removed by rotary evaporation
  2. customthe residue partitioned between chloroform and 1M sodium hydroxide
  3. customThe layers were separated
  4. dry with materialthe organic phase was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash silica gel chromatography with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-8809bc32dadf4a27a935096e4a94a211
Source dataset
uspto-grants-2001_09
Patent number
US06284757B1

Reaction notes

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