Sodium Methoxide → HCID 178450813, compound

HRID 2169466Notes

Reaction equation

HRID 2169466 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([CH2:13][C:14]([NH2:16])=[NH:15])[CH2:12][CH2:11][CH2:10][CH2:9]1.[C:17]([O:21][C:22](=[O:37])/[C:23](/O)=[C:24](\[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)/[C:25](O)=[O:26])([CH3:20])([CH3:19])[CH3:18].C[O-].[Na+]>CO>[C:17]([O:21][C:22]([C:23]1[C:24]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[C:25]([OH:26])[N:16]=[C:14]([CH2:13][C:8]2([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][N:2]=3)[CH2:12][CH2:11][CH2:10][CH2:9]2)[N:15]=1)=[O:37])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 86725882(E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl esterHCID 867260932-(1-Pyridin-2-yl-cyclopentyl)-acetamidine hydrochloride

Product 1

HCID 178450813HCID 178450813, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-(1-pyridin-2-yl-cyclopentyl)-acetamidine hydrochloride (435) (1 g, 3.55 mmol) and 2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester 1-methyl ester (4) (1.638 g, 5.319 mmol) in methanol (15 mL), sodium methoxide (25% in methanol) (2.3 mL, 10.638 mmol) was dropwise added at 0° C. Then reaction mixture was allowed to stir at room temperature for 16 h. Then reaction mixture was quenched with aqueous HCl (1N; 5 mL) and the methanol was removed under reduced pressure. The residue was diluted with water (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic part was dried, concentrated and the residue was purified by nor mal silica gel (100-200 mesh) column chromatography using 30% ethyl acetate in hexane as eluent to obtain 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid tert-butyl ester (436) (1.2 g, 73%) as a yellow sticky liquid.

Workup

  1. customThen reaction mixture
  2. customThen reaction mixture
  3. customwas quenched with aqueous HCl (1N; 5 mL)
  4. customthe methanol was removed under reduced pressure
  5. additionThe residue was diluted with water (20 mL)
  6. extractionextracted with ethyl acetate (2×50 mL)
  7. customThe combined organic part was dried
  8. concentrationconcentrated
  9. customthe residue was purified by nor mal silica gel (100-200 mesh) column chromatography

Sources & evidence

ORD record
ord-d651b67da25647b89bb387f95201941e
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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