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

HRID 1916410Notes

Reaction equation

HRID 1916410 reaction equation
BrC1C=CC(C([O:8][C@@H:9]2[C:13]3[N:14]=[CH:15][N:16]=[C:17]([N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]4)[C:12]=3[C@H:11]([CH3:31])[CH2:10]2)=O)=CC=1.O.O.[OH-].[Li+]>C1COCC1>[OH:8][C@@H:9]1[C:13]2[N:14]=[CH:15][N:16]=[C:17]([N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[C:12]=2[C@H:11]([CH3:31])[CH2:10]1

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 66845393HCID 66845393, compound

Product 1

HCID 59580357tert-Butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylateYield 101.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide hydrate (0.779 mL, 28.0 mmol) was added to a solution of tert-butyl 4-((5R,7R)-7-(4-bromobenzoyloxy)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (5.8 g, 11.2 mmol) in THF:H2O (150 mL, 2:1) at 0° C. The mixture was allowed to warm to room temperature and stirred at for 1 hour. The mixture was concentrated in vacuo, taken up into saturated sodium bicarbonate (100 mL) and extracted into EtOAc (2×200 mL). The reaction was dried over Na2SO4 and concentrated in vacuo to give tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (3.8 g, 11.4 mmol, 100% yield) as a foam. Similarly, tert-butyl 4-((5R,7S)-7-(4-bromobenzoyloxy)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (1.29 g, 2.49 mmol) was dissolved in THF:H2O (10 mL, 2:1), cooled to 0° C. and then treated with solid lithium hydroxide hydrate. The solution was stirred at ambient temperature for 16 hours. The reaction was quenched with saturated NH4Cl and concentrated in vacuo. The resulting residue was diluted with ethyl acetate and a small amount of water. The layers were separated, and the aqueous layer was washed with ethyl acetate. The combined organic layers were washed with saturated NaHCO3 (2×), saturated NaCl, dried over Na2SO4 and concentrated in vacuo. The resulting residue was dried under high vacuum to give tert-butyl 4-((5R,7S)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate as a foam (0.843 g, 100%).

Workup

  1. customThe reaction was quenched with saturated NH4Cl
  2. concentrationconcentrated in vacuo
  3. additionThe resulting residue was diluted with ethyl acetate
  4. customThe layers were separated
  5. washthe aqueous layer was washed with ethyl acetate
  6. washThe combined organic layers were washed with saturated NaHCO3 (2×), saturated NaCl
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was dried under high vacuum

Sources & evidence

ORD record
ord-849bc3e7deee4f589dc6546fd7d120e3
Source dataset
uspto-grants-2013_12
Patent number
US08618097B2

Reaction notes

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