Triphenylmethyl phosphonium bromide → 5-ethyl-2-{4-[(1R,2S)-2-vinylcyclopropyl]piperidin-1-yl}pyrimidine

HRID 1468854Notes

Reaction equation

HRID 1468854 reaction equation
[Br-].C1([C:8]([PH3+])([C:15]2[CH:20]=[CH:19]C=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=CC=2)C=CC=CC=1.[Li]CCCC.[CH2:27]([C:29]1[CH:30]=[N:31][C:32]([N:35]2CCC([C@H]3C[C@H]3C=O)CC2)=[N:33][CH:34]=1)[CH3:28]>C1COCC1>[CH2:27]([C:29]1[CH:30]=[N:31][C:32]([N:35]2[CH2:17][CH2:16][CH:15]([C@H:8]3[CH2:9][C@H:14]3[CH:13]=[CH2:12])[CH2:20][CH2:19]2)=[N:33][CH:34]=1)[CH3:28]

Participants

5

Reactant 3

HCID 21951224Triphenylmethyl phosphonium bromideHCID 89297337(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropanecarbaldehydeHCID 178418339Butyllithium

Product 1

HCID 892973365-ethyl-2-{4-[(1R,2S)-2-vinylcyclopropyl]piperidin-1-yl}pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.), stirred suspension of triphenylmethyl phosphonium bromide (10.5 g, 29.4 mmol) in THF (80 mL) was added n-BuLi (11.4 mL of a 2.5M solution in hexanes, 28.4 mmol) dropwise. Upon stirring the resulting orange suspension for 45 min at −78° C., a solution of the product of step B (3.8 g, 14.7 mmol) in THF (25 mL) was added dropwise. The cold bath was removed and the mixture was stirred at RT for 2 h before being quenched with a saturated aqueous solution of NH4Cl. The organic layer was separated and the aqueous layer was extracted with Et2O (3×). The combined organic layers were washed with brine (1×), dried over anhydrous MgSO4, filtered, and concentrated under vacuum to leave a residue which was purified by column chromatography on silica (elution with 5:1 hexane:ethyl acetate) to yield the desired alkene. MS (ESI) m/z 258 [M+H]+.

Workup

  1. stirringUpon stirring the resulting orange suspension for 45 min at −78° C.
  2. customThe cold bath was removed
  3. stirringthe mixture was stirred at RT for 2 h
  4. custombefore being quenched with a saturated aqueous solution of NH4Cl
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with Et2O (3×)
  7. washThe combined organic layers were washed with brine (1×)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customto leave a residue which
  12. customwas purified by column chromatography on silica (elution with 5:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-6390cf619c614678a6021b4a19fbc70b
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

Loading…