Methanol → HCID 178524865, compound

HRID 2169304Notes

Reaction equation

HRID 2169304 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:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:33][CH2:32][C:27]3([O:31][CH2:30][CH2:29][O:28]3)[CH2:26][CH2:25]2)[N:9]=1)=[O:7])(C)(C)C.O[Li].O.CO.ClCCl>O1CCCC1.O>[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:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:25][CH2:26][C:27]3([O:28][CH2:29][CH2:30][O:31]3)[CH2:32][CH2:33]2)=[N:11][C:12]=1[OH:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6344DichloromethaneHCID 168937Lithium hydroxide, monohydrateHCID 178450805HCID 178450805, compound

Product 1

HCID 178524865HCID 178524865, compoundYield 92.05%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

A mixture of 5-benzyloxy-6-hydroxy-2-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-ylmethyl)-pyrimidine-4-carboxylic acid tert-butyl ester (269) (850 mg, 1.60 mmol), LiOH.H2O (670 mg, 15.96 mmol) in tetrahydrofuran-water (5:1, 48 mL) was refluxed for 20 h while silica thin layer chromatography was performed (methanol:dichloromethane=1:9, Rf=0.1). Tetrahydrofuran was removed from the reaction mixture in vacuo and the residue was diluted with water (25 mL), cooled in ice water, neutralized to about pH 7 with 1N aqueous HCl and extracted with ethyl acetate (2×50 mL). The combined organic parts were washed with brine (25 mL), dried and concentrated in vacuo to get pure 5-benzyloxy-6-hydroxy-2-(8-phenyl-1,4-dioxa-spiro[4.5]dec-8-ylmethyl)-pyrimidine-4-carboxylic acid (270) (700 mg, 92.05%) as a yellow solid.

Workup

  1. temperaturewas refluxed for 20 h while silica thin layer chromatography
  2. customTetrahydrofuran was removed from the reaction mixture in vacuo
  3. additionthe residue was diluted with water (25 mL)
  4. temperaturecooled in ice water
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. washThe combined organic parts were washed with brine (25 mL)
  7. customdried
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c885ba0fcdf94dc88a573426dfa03d36
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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