Reaction #1531310

Reaction equation

P(t-bu)3

lithium dicyclohexyl amide

acetic acid tert-butyl ester

4-[4-(5-bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine

→

ester

(6-{4-[6-(4-Fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-methyl-pyridin-3-yl)-acetic acid tert-butyl ester

Solvents

toluene

Conditions

Workup

1. 1
   OtherDe-gas the suspension for 5 min
2. 2
   workup.STIRRINGstir for 16 h at room temperature
3. 3
   workup.ADDITIONDilute with EtOAc
4. 4
   Washwash with brine
5. 5
   Dryingdry the organic layer (Na2SO4)
6. 6
   Concentrationconcentrate under reduced pressure
7. 7
   OtherPurify
8. 8
   Washeluting with EtOAc-Hexanes (1:4)

Procedure

To lithium dicyclohexyl amide add a solution of acetic acid tert-butyl ester (62 μL, 0.46 mmol) in toluene (2 mL). Stir for 10 min at room temperature, and then add 4-[4-(5-bromo-3-methyl-pyridin-2-yl)-2-(R)-methyl-piperazin-1-yl]-6-(4-fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine (200 mg, 0.38 mmol), Pd2(dba)3 (3.5 mg, 1%) and P(t-bu)3 (0.8 mg, 1%). De-gas the suspension for 5 min and stir for 16 h at room temperature. Dilute with EtOAc, wash with brine, dry the organic layer (Na2SO4) and concentrate under reduced pressure. Purify using flash chromatography eluting with EtOAc-Hexanes (1:4) to give the title ester.

Source