Benzoic Acid → (7S,8aS)-2-(5-Fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazin-7-yl benzoate

HRID 861345Notes

Reaction equation

HRID 861345 reaction equation
[OH:1][C@H:2]1[CH2:17][N:5]2[CH2:6][CH2:7][N:8]([C:10]3[N:15]=[CH:14][C:13]([F:16])=[CH:12][N:11]=3)[CH2:9][C@@H:4]2[CH2:3]1.[C:18](O)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[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>C1COCC1.CO.C(Cl)Cl>[C:18]([O:1][C@@H:2]1[CH2:17][N:5]2[CH2:6][CH2:7][N:8]([C:10]3[N:11]=[CH:12][C:13]([F:16])=[CH:14][N:15]=3)[CH2:9][C@@H:4]2[CH2:3]1)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 243Benzoic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 15886074(7R,8aS)-7-hydroxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine

Product 1

HCID 15886068(7S,8aS)-2-(5-Fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazin-7-yl benzoateYield 59%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2.0 g (8.4 mmol) of (7R,8aS)-7-hydroxy-2-(5-fluoropyrimidin-2-yl)-1,2,3,4,6,7,8,8a-octahydro-pyrrolo[1,2-a]pyrazine (Preparation 6), 1.54 g (12.6 mmol) of benzoic acid, 2.65 g (10.1 mmol) of triphenylphosphine, and 1.59 mL (10.1 mmol) of diethyl azodicarboxylate (DEAD) in 85 mL of THF was stirred at ambient temperature for 16 h. The solvent was evaporated, and flash silica gel chromatography with 1:1 hexane:ethyl acetate gave 2.5 g of partially purified material. A second chromatography with 10:1 methylene chloride:methanol gave 1.68 g (59%) of the title compound. mp (.HCl) 134°-135.5° C. 13C NMR (base, CDCl3): δ 36.1, 43.7, 48.7, 51.2, 60.4, 61.8, 73.2, 128.3, 129.7, 130.1, 133.0, 145.0, 145.3, 150.0, 153.1. 158.9, 166.7. HRMS calcd for C18H20FN4O (MH+): 343.1570, found: 343.1585.

Workup

  1. customThe solvent was evaporated
  2. customflash silica gel chromatography with 1:1 hexane:ethyl acetate gave 2.5 g of partially purified material

Sources & evidence

ORD record
ord-3dbee258c2c4480ab179da65b901b958
Source dataset
uspto-grants-1998_02
Patent number
US05714487

Reaction notes

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