Ethyl Acetate → HCID 178450822, compound

HRID 2169234Notes

Reaction equation

HRID 2169234 reaction equation
[C:1]1([C:7]2[C:8]([CH2:13][C:14]([NH2:16])=[NH:15])=[N:9][CH:10]=[CH:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=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+].C(OCC)(=O)C>CO.CCCCCC>[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:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:12][CH:11]=[CH:10][N:9]=2)[N:15]=1)=[O:37])([CH3:20])([CH3:18])[CH3:19]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10942334Sodium MethoxideHCID 867258802-(3-Phenyl-pyridin-2-yl)-acetamidineHCID 86725882(E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester

Product 1

HCID 178450822HCID 178450822, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8058HexaneSolvent

Procedure

To a stirred solution of 2-(3-phenyl-pyridin-2-yl)-acetamidine (162) (300 mg, 1.10 mmol) and (E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester (4) (511 mg, 1.66 mmol) in methanol (5 mL) was added sodium methoxide (1.3 mL, 3.32 mmol) at 0° C., then the reaction mixture was allowed to warm to room temperature, stirred for 16 h. Silica thin layer chromatography was performed (50% ethyl acetate in hexane, Rf=0.3). After completion of the reaction, it was quenched with water, methanol was evaporated and water (30 mL) was added. The mixture was extracted with ethyl acetate (3×30 mL) and the separated organic part was dried and concentrated to get a crude product, which was purified by a CombiFlash column (eluted at 90% ethyl acetate in hexane) to get 5-benzyloxy-6-hydroxy-2-(3-phenyl-pyridin-2-ylmethyl)-pyrimidine-4-carboxylic acid tert-butyl ester (163) (250 mg, 48.1%) as a yellow sticky product.

Workup

  1. customAfter completion of the reaction, it
  2. customwas quenched with water, methanol
  3. customwas evaporated
  4. additionwater (30 mL) was added
  5. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  6. customthe separated organic part was dried
  7. concentrationconcentrated
  8. customto get a crude product, which
  9. customwas purified by a CombiFlash column (eluted at 90% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-1d328b6d972445f8a104422304cd2968
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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