Proton sponge → 3-(3-Methoxy-propoxy)-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester

HRID 852639Notes

Reaction equation

HRID 852639 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])[CH:7]=[C:6]([O:16][CH2:17][CH2:18][CH2:19][OH:20])[CH:5]=1.[CH3:22]N(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.F[B-](F)(F)F.C[O+](C)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])[CH:7]=[C:6]([O:16][CH2:17][CH2:18][CH2:19][O:20][CH3:22])[CH:5]=1

Participants

5

Reactant 3

HCID 88675Proton sponge2×HCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)2×HCID 693569733-(3-Hydroxy-propoxy)-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester

Product 1

HCID 693602353-(3-Methoxy-propoxy)-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(3-Hydroxy-propoxy)-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (B15) (127 mg, 0.43 mmol, 1 equiv) in CH2Cl2 (2 ml) was treated with proton sponge (279 mg, 1.30 mmol, 3 equiv) and trimethyloxonium tetrafluoroborate (192 mg, 1.30 mmol, 3 equiv). After 3 hrs, further quantities of proton sponge (93 mg, 0.43 mmol, 1 equiv) and trimethyloxonium tetrafluoroborate (65 mg, 0.43 mmol, 1 equiv) were added and stirring was continued for a further 2 h. The mixture was then partitioned between AcOEt and 2N aqueous HCl solution. The two layers were separated and the aqueous phase extracted with AcOEt. The combined organic layers were washed with saturated aqueous NaHCO3 solution, 2N aqueous HCl solution and brine and then dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography on silica gel (ethyl acetate/iso-hexane: 1/4 to 1/3) gave 3-(3-methoxy-propoxy)-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (B17) (76 mg, 58%). [M+H]+=308.1

Workup

  1. waitwas continued for a further 2 h
  2. customThe mixture was then partitioned between AcOEt and 2N aqueous HCl solution
  3. customThe two layers were separated
  4. extractionthe aqueous phase extracted with AcOEt
  5. washThe combined organic layers were washed with saturated aqueous NaHCO3 solution, 2N aqueous HCl solution and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification by flash chromatography on silica gel (ethyl acetate/iso-hexane: 1/4 to 1/3)

Sources & evidence

ORD record
ord-68ab91a83d1243f387007897183ef212
Source dataset
uspto-grants-2007_08
Patent number
US07253198B2

Reaction notes

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