Tetrahydrofuran → HCID 69430054, compound

HRID 1977017Notes

Reaction equation

HRID 1977017 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3]C.[CH:6]([C@H:8]1[CH2:24][N:12]2[CH2:13][CH2:14][N:15]([C:17]3[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=3)[CH2:16][C@@H:11]2[CH2:10][CH2:9]1)=O.[CH2:25]1[CH2:29]O[CH2:27][CH2:26]1>[Cl-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1>[C:25]1([CH:29]=[CH:6][CH:8]2[CH2:24][N:12]3[CH2:13][CH2:14][N:15]([C:17]4[N:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=4)[CH2:16][CH:11]3[CH2:10][CH2:9]2)[CH:3]=[CH:2][CH:1]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 57161266HCID 57161266, compoundHCID 178418339Butyllithium

Product 1

HCID 69430054HCID 69430054, compound

Reagents, catalysts & solvents 1

HCID 70671Benzyltriphenylphosphonium chlorideCatalyst

Procedure

A solution of 1.70 g (4.38 mmol) of benzyl triphenyl phosphonium chloride in 20 mL of dry THF was chilled to −78° C. and treated with 1.75 mL (4.38 mmol) of n-butyllithium (2.5 M in hexane). After 15 min, 1.05 g (3.98 mmol) of (7R,9aS)-7-formyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine in 20 mL of dry THF was added dropwise over 30 min, the cooling bath was removed and the solution allowed to warm slowly to ambient temperature overnight (16 h). The solution was concentrated in vacuo and the residue was partitioned between ethyl ether and water. The organic layer was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with petroleum ether:ethyl ether in ratios from 4:1 to 3:1 gave the following isomers of 7-(2-phenyl)ethenyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine: E-(7S,9aS), 0.19 g (Rf=0.75 with 3:1 hexane:ethyl acetate); Z-(7R,9aS), 0.16 g (Rf=0.47 with 3:1 hexane:ethyl acetate); E-(7R,9aS), 0.46 g (Rf=23 with 3:1 hexane:ethyl acetate).

Workup

  1. customthe cooling bath was removed
  2. concentrationThe solution was concentrated in vacuo
  3. customthe residue was partitioned between ethyl ether and water
  4. dry with materialThe organic layer was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customPurification by flash silica gel chromatography with petroleum ether

Sources & evidence

ORD record
ord-16fd50ce3a08404a8318e415b4397d58
Source dataset
uspto-grants-2001_05
Patent number
US06231833B1

Reaction notes

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