Ethyl Acetate → HCID 178524870, compound

HRID 2169283Notes

Reaction equation

HRID 2169283 reaction equation
C([O:5][C:6]([C:8]1[C:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:12]([OH:22])[N:11]=[C:10]([CH2:23][C:24]2([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)[CH2:28][CH2:27][CH2:26][CH2:25]2)[N:9]=1)=[O:7])(C)(C)C.O1CCCC1.O.C(OCC)(=O)C>CCCCCC>[CH2:15]([O:14][C:13]1[C:8]([C:6]([OH:7])=[O:5])=[N:9][C:10]([CH2:23][C:24]2([C:29]3[CH:30]=[CH:31][C:32]([C:35]([F:37])([F:38])[F:36])=[CH:33][CH:34]=3)[CH2:28][CH2:27][CH2:26][CH2:25]2)=[N:11][C:12]=1[OH:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21881883Oxolane--water (1/1)HCID 178450810HCID 178450810, compound

Product 1

HCID 178524870HCID 178524870, compoundYield 99.8%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To a stirred solution 5-benzyloxy-6-hydroxy-2-[1-(4-trifluoromethyl-phenyl)-cyclopentylmethyl]-pyrimidine-4-carboxylic acid tert-butyl ester (243) (250 mg, 0.53 mmol) in the mixture of tetrahydrofuran-water (2:1, 10 mL) was added lithium-hydroxide monohydrate (477 mg, 11.36 mmol) and the reaction mixture was refluxed for 20 h. Very small amounts of the starting ester remained. Silica thin layer chromatography was performed (50% ethyl acetate in hexane, Rf=0.1). Volatiles were evaporated, water added (10 mL) and the aqueous part was extracted with ethyl acetate (2×3 0 mL). The ethyl acetate part was thereafter discarded and the aqueous part was acidified with 1N HCl to a pH of about 5-6. The acidified aqueous part was extracted with ethyl acetate (3×30 mL), dried and concentrated to get 5-benzyloxy-6-hydroxy-2-[1-(4-trifluoromethyl-phenyl)-cyclopentylmethyl]-pyrimidine-4-carboxylic acid (244) (250 mg, 93.13%) as an off-white solid.

Workup

  1. additionwas added lithium-hydroxide monohydrate (477 mg, 11.36 mmol)
  2. temperaturethe reaction mixture was refluxed for 20 h
  3. customVolatiles were evaporated
  4. additionwater added (10 mL)
  5. extractionthe aqueous part was extracted with ethyl acetate (2×3 0 mL)
  6. extractionThe acidified aqueous part was extracted with ethyl acetate (3×30 mL)
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-68017033a9b441d69871f9e63c3106f8
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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