Sodium Methoxide → HCID 178450807, compound

HRID 2169292Notes

Reaction equation

HRID 2169292 reaction equation
[C:1]1([C:7]2([CH2:13][C:14]([NH2:16])=[NH:15])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[O:18][C:19](=O)/[C:20](/[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[C:21](\O)/[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].C[O-].[Na+]>CO.ClCCl>[C:25]([O:24][C:22]([C:21]1[C:20]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:19]([OH:18])[N:16]=[C:14]([CH2:13][C:7]2([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[N:15]=1)=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 546790054-Tert-butyl 1-methyl 2-(benzyloxy)-3-hydroxyfumarateHCID 867259372-(1-Phenyl-cyclohexyl)-acetamidine

Product 1

HCID 178450807HCID 178450807, compoundYield 85.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of HCl-salt of 2-(1-phenyl-cyclohexyl)-acetamidine (254) (2.0 g, 7.91 mmol) and (E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester 1-methyl ester (9) (3.66 g, 11.86 mmol) in methanol (50.0 mL) was added sodium methoxide (1.28 g, 23.73 mmol, 25% in methanol) at 0° C. Then the reaction mixture was allowed to warm up to room temperature and was stirred for 16 h. After completion of the reaction, the solvent was reduced and the crude product was dissolved in dichloromethane and the resultant mixture extracted with dichloromethane. The organic layer was washed with 1N HCl and with water and brine. It was then dried over Na2SO4 and concentrated. The crude product was purified by normal silica gel column chromatography (using 10% ethyl acetate in hexane) to get 5-benzyloxy-6-hydroxy-2-(1-phenyl-cyclohexylmethyl)-pyrimidine-4-carboxylic acid tert-butyl ester (255) (3.2 g, 85.0%) as a yellowish thick liquid which turned into a solid after storing at room temperature.

Workup

  1. customAfter completion of the reaction
  2. extractionthe resultant mixture extracted with dichloromethane
  3. washThe organic layer was washed with 1N HCl and with water and brine
  4. dry with materialIt was then dried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by normal silica gel column chromatography (using 10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-b3f02e5602d2400e84462248455039fc
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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