Methanol → (R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

HRID 1675870Notes

Reaction equation

HRID 1675870 reaction equation
C([O:4][CH:5]1[C:9]2[N:10]=[CH:11][N:12]=[C:13]([N:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:8]=2[C@H:7]([CH3:27])[CH2:6]1)(=O)C.[Li+].[OH-].O.CO>C1COCC1>[OH:4][CH:5]1[C:9]2[N:10]=[CH:11][N:12]=[C:13]([N:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]3)[C:8]=2[C@H:7]([CH3:27])[CH2:6]1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 59580360(R)-tert-butyl 4-(7-acetoxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate

Product 1

HCID 59580348(R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-tert-butyl 4-(7-acetoxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (1.16 g, 3.08 mmol) in 12 mL THF was added 3M LiOH (2.57 mL, 7.70 mmol) and 3 mL H2O. The reaction mixture was stirred at room temperature for 15 hours, after which H20 was added, and the mixture was extracted with 3×75 mL EtOAc. The combined extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude was purified on silica gel (Biotage 40S) first with 1:1 to 1:6 DCM:EtOAC gradient, followed by 20:1 DCM:MeOH to give (R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (0.556 g, 54.0% yield) as a 1:1 mixture of diastereomers as a brown foam. MS (APCI+) m/z 335 [M+H]+.

Workup

  1. additionafter which H20 was added
  2. extractionthe mixture was extracted with 3×75 mL EtOAc
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified on silica gel (Biotage 40S) first with 1:1 to 1:6 DCM

Sources & evidence

ORD record
ord-729e9cc57982416fb6caf1dd1d0c8801
Source dataset
uspto-grants-2011_08
Patent number
US08003651B2

Reaction notes

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