Methyl 4-oxooxolane-3-carboxylate → HCID 178517510, compound

HRID 1010848Notes

Reaction equation

HRID 1010848 reaction equation
CO[C:3]([CH:5]1[C:9](=O)[CH2:8][O:7][CH2:6]1)=[O:4].[F:11][C:12]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:13]=1[C:14]([NH2:16])=[NH:15]>C(O)C>[Cl:21][C:18]1[CH:19]=[CH:20][C:12]([F:11])=[C:13]([C:14]2[N:16]=[C:3]([OH:4])[C:5]3[CH2:6][O:7][CH2:8][C:9]=3[N:15]=2)[CH:17]=1

Participants

4

Reactant 2

HCID 14666564Methyl 4-oxooxolane-3-carboxylateHCID 219309795-Chloro-2-fluorobenzene-1-carboximidamide

Product 1

HCID 178517510HCID 178517510, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
80 °C

Procedure

To a suspension of 4-oxo-tetrahydrofuran-3-carboxylic acid methyl ester (prepared according to Dowd, P.; Choi, S-C. Tetrahedron, 1991, 47, 4847-4860; 800 mg, 5.55 mmol, 1 eq) in ethanol (20 ml) was added a solution of 2-fluoro-5-chloro-benzamidine (961 mg, 5.55 mmol, 1 eq) in EtOH (10 ml). The reaction mixture was heated to 80° C. overnight. The reaction mixture was cooled to r.t. and the white precipitate was filtered and washed with cold ethyl actetate (2×20 ml). The crude residue was partitioned between chloroform and water. The aqueous layer was acidified to pH 4 and the product was extracted with chloroform (3×50 ml). The organic layers were combined, washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a crude solid which was purified by flash column chromatography (5% MeOH in EtOAc) to give a white solid 2-(5-chloro-2-fluoro-phenyl)-5,7-dihydrofuro[3,4-d]pyrimidin-4-ol (440 mg, 30%).

Workup

  1. temperatureThe reaction mixture was cooled to r.t.
  2. filtrationthe white precipitate was filtered
  3. washwashed with cold ethyl
  4. customThe crude residue was partitioned between chloroform and water
  5. extractionthe product was extracted with chloroform (3×50 ml)
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a crude solid which
  11. customwas purified by flash column chromatography (5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-5cc79a88f58a455691c2e5528ec43b50
Source dataset
uspto-grants-2011_07
Patent number
US07977342B2

Reaction notes

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