HCID 10928782, compound → HCID 86746696, compound

HRID 1590080Notes

Reaction equation

HRID 1590080 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=[C:15](Br)Br)=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=[C:10]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:9]=2)=[CH:4][CH:3]=1.C([Li])CCC.[CH3:32][O:33][P:34](Cl)([CH2:36][C@@H:37]([O:43][Si:44]([C:57]([CH3:60])([CH3:59])[CH3:58])([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH2:38][C:39]([O:41][CH3:42])=[O:40])=[O:35]>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]#[C:15][P:34]([O:33][CH3:32])([CH2:36][C@@H:37]([O:43][Si:44]([C:57]([CH3:58])([CH3:60])[CH3:59])([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=3)[CH2:38][C:39]([O:41][CH3:42])=[O:40])=[O:35])=[C:12]([CH:18]([CH3:20])[CH3:19])[N:11]=[C:10]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10928782HCID 10928782, compoundHCID 19769494HCID 19769494, compoundHCID 178418339Butyllithium

Product 1

HCID 86746696HCID 86746696, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

In a separate flask, a solution of 4-(4-fluorophenyl)-6-(1-methylethyl)-2-phenyl-5-(2,2-dibromovinyl)-pyrimidine obtained in step (v) above (1.000 gm, 2.10 mmol) in tetrahydrofuran (THF) (10 ml) was added dropwise to a -78° C. THF solution (15 ml) of n-butyl lithium (nBuLi) (2.5M in hexane, 1.68 ml, 4.20 mmol). The solution was allowed to stir 1 hour at -78° C., then cannulated into a THF solution (20 ml) of (S)-4-(methoxychlorophosphinyl)-3-[[(t-butyl)diphenylsilyl]-oxy]butanoic acid, methyl ester obtained in step (f) above which had also been cooled to -78° C. The resultant solution was stirred for 30 minutes, then quenched with saturated NH4Cl (15 ml) and warmed to 0° C. Then, saturated NaHCO3 was added to the solution which was subsequently warmed to room temperature. The mixture was diluted with ether and the organic layer was washed with brine, then dried over Na2SO 4, filtered and concentrated to give an orange oil. The oil was purified by flash chromatography on Merck silica gel in 30-50% EtOAc in hexane. The desired fractions were combined and evaporated to afford the title compound as yellow foam (0.732 gm, 49%). TLC: Rf =0.50 (50% EtOAc in hexane).

Workup

  1. temperaturehad also been cooled to -78° C
  2. customquenched with saturated NH4Cl (15 ml)
  3. temperaturewarmed to 0° C
  4. additionThen, saturated NaHCO3 was added to the solution which
  5. temperaturewas subsequently warmed to room temperature
  6. additionThe mixture was diluted with ether
  7. washthe organic layer was washed with brine
  8. dry with materialdried over Na2SO 4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give an orange oil
  12. customThe oil was purified by flash chromatography on Merck silica gel in 30-50% EtOAc in hexane
  13. customevaporated

Sources & evidence

ORD record
ord-a68014d12399489d8ad49cdd35a7d536
Source dataset
uspto-grants-1993_04
Patent number
US05202327

Reaction notes

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