Ethyl Acetate → HCID 178450820, compound

HRID 2169408Notes

Reaction equation

HRID 2169408 reaction equation
Cl.[Br:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[CH2:10][C:11]([NH2:13])=[NH:12].[C:14]([O:18][C:19](=[O:34])/[C:20](/O)=[C:21](\[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)/[C:22](O)=[O:23])([CH3:17])([CH3:16])[CH3:15].C[O-].[Na+].C(OCC)(=O)C>CO.CCCCCC.O>[C:14]([O:18][C:19]([C:20]1[C:21]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:22]([OH:23])[N:13]=[C:11]([CH2:10][C:4]2[CH:5]=[CH:6][C:7]([Cl:9])=[CH:8][C:3]=2[Br:2])[N:12]=1)=[O:34])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10942334Sodium MethoxideHCID 86725882(E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl esterHCID 867260392-(2-Bromo-4-chlorophenyl)-acetamidine hydrochloride

Product 1

HCID 178450820HCID 178450820, compoundYield 47.95%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8058HexaneSolvent

Procedure

To a stirred solution of 2-(2-bromo-4-chlorophenyl)-acetamidine hydrochloride (375) (7 g, 24.823 mmol) and 2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester 1-methyl ester (4) (11.47 g, 37.23 mmol) in methanol (100 mL) was dropwise added sodium methoxide (16.1 mL) (25% in methanol) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 16 h while silica thin layer chromatography was performed (50% ethyl acetate in hexane; Rf=0.5). The reaction mixture was quenched with 1N HCl (5 mL) and the methanol was removed under reduced pressure to yield a residue which was diluted with water (200 mL) and extracted with ethyl acetate (2×250 mL). The combined organic parts were dried and concentrated. The obtained crude product was purified by normal silica (100-200 mesh) column to get 5-benzyloxy-2-(2-bromo-4-chlorobenzyl)-6-hydroxypyrimidine-4-carboxylic acid tert-butyl ester (376) (6.02 g, 47.95%) as a white solid.

Workup

  1. customat 0° C
  2. customThe reaction mixture was quenched with 1N HCl (5 mL)
  3. customthe methanol was removed under reduced pressure
  4. customto yield a residue which
  5. extractionextracted with ethyl acetate (2×250 mL)
  6. customThe combined organic parts were dried
  7. concentrationconcentrated
  8. customThe obtained crude product
  9. customwas purified by normal silica (100-200 mesh) column

Sources & evidence

ORD record
ord-13149ec64ba64d64b4b157553daf7228
Source dataset
uspto-grants-2015_06
Patent number
US09045486B2

Reaction notes

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