Methanol → 2-(2-Chloro-3-ethynyl-phenoxy)-butyrimidic acid methyl ester

HRID 1254973Notes

Reaction equation

HRID 1254973 reaction equation
[Cl:1][C:2]1[C:13]([CH:14]=O)=[CH:12][CH:11]=[CH:10][C:3]=1[O:4][CH:5]([CH2:8][CH3:9])[C:6]#[N:7].[C:16]([O-:19])([O-])=O.[K+].[K+].O.[CH3:23]O>>[CH3:16][O:19][C:6](=[NH:7])[CH:5]([O:4][C:3]1[CH:10]=[CH:11][CH:12]=[C:13]([C:14]#[CH:23])[C:2]=1[Cl:1])[CH2:8][CH3:9]

Participants

5

Reactant 4

HCID 887MethanolHCID 962WaterHCID 11430Potassium CarbonateHCID 595657782-(2-Chloro-3-formyl-phenoxy)-butyronitrile

Product 1

HCID 595657822-(2-Chloro-3-ethynyl-phenoxy)-butyrimidic acid methyl ester

Conditions

Temperature
0 °C

Procedure

Dimethyl-1-diazo-2-oxypropylphosphonate (0.48 g, 2.5 mmol) was added to a solution of 2-(2-chloro-3-formyl-phenoxy)-butyronitrile (0.4 g, 1.8 mmol) in MeOH (40 ml) at room temperature under argon. The solution was cooled to 0° C. and K2CO3 was added. After the addition stirring was continued for 48 h at room temperature. Reaction mixture was then poured into cold water (0° C.) and extracted twice with ethylacetate. The combined organic layers were dried with MgSO4 and evaporated. The crude product was chromatographed on silica with ethylacetate/cyclohexane to yield 2-(2-chloro-3-ethynyl-phenoxy)-butyrimidic acid methyl ester (0.32 g, light yellow oil); 1H-NMR (CDCl3) 1.05 t, 3H, 1.85-2.03 m, 2H, 3.39, s, 1H, 4.52 dd, 1H, 6.78 d, 1H, 7.12 t, 1H, 7.19 d, 1H, 7.72, br s, 1H.

Workup

  1. additionAfter the addition
  2. customReaction mixture
  3. extractionextracted twice with ethylacetate
  4. dry with materialThe combined organic layers were dried with MgSO4
  5. customevaporated
  6. customThe crude product was chromatographed on silica with ethylacetate/cyclohexane

Sources & evidence

ORD record
ord-644dbefe788947b295b280cf77c7d4c6
Source dataset
uspto-grants-2013_06
Patent number
US08455663B2

Reaction notes

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