Hydrochloric Acid → (7S,8aS)-7-(4-fluorophenoxy)-2-phenylmethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

HRID 861341Notes

Reaction equation

HRID 861341 reaction equation
[OH:1][C@H:2]1[CH2:17][N:5]2[CH2:6][CH2:7][N:8]([CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:9][C@@H:4]2[CH2:3]1.[F:18][C:19]1[CH:24]=[CH:23][C:22](O)=[CH:21][CH:20]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.Cl>C1COCC1.C(OCC)C>[F:18][C:19]1[CH:24]=[CH:23][C:22]([O:1][C@@H:2]2[CH2:17][N:5]3[CH2:6][CH2:7][N:8]([CH2:10][C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH2:9][C@@H:4]3[CH2:3]2)=[CH:21][CH:20]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 97324-FluorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 14914621(7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol

Product 1

HCID 57170166(7S,8aS)-7-(4-fluorophenoxy)-2-phenylmethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazineYield 95.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.971 g (4.18 mmol) of (7R,8aS)-7-hydroxy-2-phenylmethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Diafi, L.; et al. J. Het. Chem., 1990, 27, 2181), 0.703 g (6.27 mmol) of 4-fluorophenol and 1.32 g (5.02 mmol) of triphenylphosphine in 20 mL of dry THF was treated with 0.79 mL (5.02 mmol) of diethyl azodicarboxylate and the solution stirred at room temperature for 21 h. Excess HCl (g) in diethyl ether was added, the precipitate was collected on a Buchner funnel, washing with ethyl acetate. The gummy residue was dissolved in a mixture of ethyl acetate and aqueous ammonium hydroxide, the layers were separated, the aqueous phase was extracted with more ethyl acetate (2×), the combined organic phase was dried (magnesium sulfate), filtered and evaporated. Purification by silica gel MPLC with 95:5 ethyl acetate:methanol gave 1.3 g (95%) of (7S,8aS)-7-(4-fluorophenoxy)-2-phenylmethyl-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine.

Workup

  1. customthe precipitate was collected on a Buchner funnel
  2. washwashing with ethyl acetate
  3. dissolutionThe gummy residue was dissolved in a mixture of ethyl acetate and aqueous ammonium hydroxide
  4. customthe layers were separated
  5. extractionthe aqueous phase was extracted with more ethyl acetate (2×)
  6. dry with materialthe combined organic phase was dried (magnesium sulfate)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by silica gel MPLC with 95:5 ethyl acetate

Sources & evidence

ORD record
ord-ab599bbd4ac44c6aa0924419c0b20142
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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