Dichloromethane → (s)-3-[4-(2-Tert-butyl-6-cyclobutyl-pyrimidin-4-yl)piperazin-1-yl]-2-methyl-propan-1-ol

HRID 219710Notes

Reaction equation

HRID 219710 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C@H:18]([CH3:24])[CH2:19][O:20]C(=O)C)[CH2:13][CH2:12]2)[CH:8]=[C:7]([CH:25]2[CH2:28][CH2:27][CH2:26]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].ClCCl>C(O)C.O>[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:12][CH2:13][N:14]([CH2:17][C@H:18]([CH3:24])[CH2:19][OH:20])[CH2:15][CH2:16]2)[CH:8]=[C:7]([CH:25]2[CH2:28][CH2:27][CH2:26]2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 131729779(S)-Acetic acid 3-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-2-methyl-propyl ester

Product 1

HCID 69025560(s)-3-[4-(2-Tert-butyl-6-cyclobutyl-pyrimidin-4-yl)piperazin-1-yl]-2-methyl-propan-1-olYield 56.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
65 °C

Procedure

5.64 g of crude (S)-acetic acid 3-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-2-methyl-propyl ester (asserted 14.1 mmol) were stirred in 26.6 ml of ethanol. A solution of 2.83 g of sodium hydroxide in 6 ml of water was added and the reaction was heated at 60-70° C. for 5 h. After cooling to room temperature, 50 ml of water and 50 ml of dichloromethane were added. The dichloromethane layer was separated and the aqueous phase was extracted with a further portion dichloromethane. The combined dichloromethane extracts were washed with water, dried over magnesium sulfate, filtered and evaporated under vacuum to give an orange oil. The crude product was purified by flash column chromatography eluting with dichloromethane-methanol (9:1). The fractions containing the product were combined and evaporated to give an orange oil (2.76 g).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe dichloromethane layer was separated
  3. extractionthe aqueous phase was extracted with a further portion dichloromethane
  4. washThe combined dichloromethane extracts were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under vacuum
  8. customto give an orange oil
  9. customThe crude product was purified by flash column chromatography
  10. washeluting with dichloromethane-methanol (9:1)
  11. additionThe fractions containing the product
  12. customevaporated

Sources & evidence

ORD record
ord-1d71798a1ee24b049d26c2308285afa4
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Reaction notes

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