Tetrahydrofuran → (5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol

HRID 2192420Notes

Reaction equation

HRID 2192420 reaction equation
C([O:4][CH:5]1[C:9]2[N:10]=[CH:11][N:12]=[C:13]([Cl:14])[C:8]=2[C@H:7]([CH3:15])[CH2:6]1)(=O)C.C1COCC1.O.[OH-].[Li+]>O>[Cl:14][C:13]1[C:8]2[C@H:7]([CH3:15])[CH2:6][CH:5]([OH:4])[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 58111335(5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl acetate

Product 1

HCID 86654856(5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-olYield 63%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl acetate (11.86 g, 52.33 mmol) in 2:1 THF:H2O (270 mL) was cooled to 0° C. and treated with lithium hydroxide hydrate (3.95 g, 94.2 mmol). The reaction was stirred at room temperature for 4 hours. The reaction was concentrated and diluted with water and acidified with 6N HCl to a pH of 6. The aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried MgSO4, filtered, and concentrated. The crude residue was chromatographed (Biotage 65) eluting with 30-50% EtOAc/hexane to give (5R)-4-chloro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol (6.09 g, 63%).

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with water
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organics were washed with brine, dried MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was chromatographed (Biotage 65)
  8. washeluting with 30-50% EtOAc/hexane

Sources & evidence

ORD record
ord-c8ea0fe8da144d62b6e0754be681b4a6
Source dataset
uspto-grants-2012_12
Patent number
US08329709B2

Reaction notes

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