Trifluoroacetic acid → HCID 23512244, compound

HRID 354306Notes

Reaction equation

HRID 354306 reaction equation
[CH3:1][N:2]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1[OH:14])[C:7]([O:9][CH3:10])=[O:8])[CH3:3].C(OC([N:22]1[CH2:28][CH2:27][CH2:26][C@H:23]1[CH2:24]O)=O)(C)(C)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.C(O)(C(F)(F)F)=O>C1COCC1.C(Cl)Cl>[CH3:1][N:2]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1[O:14][CH2:24][CH:23]1[CH2:26][CH2:27][CH2:28][NH:22]1)[C:7]([O:9][CH3:10])=[O:8])[CH3:3]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 643448(S)-(-)-N-Boc-prolinolHCID 5363146Diisopropyl azodicarboxylateHCID 13724148HCID 13724148, compound

Product 1

HCID 23512244HCID 23512244, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of methyl 3-(N,N-dimethylamino)-4-hydroxybenzoate (0.817 g, 4.18 mmol), N-tert-butoxycarbonylprolinol (0.926 g, 4.60 mmol), Ph3P (1.21 g, 4.60 mmol) in THF (20 mL) was added dropwise DIAD (95%) (0.953 mL, 4.60 mmol) at 0° C. The resulting mixture was heated under reflux for 41 hr. After cooling, the mixture was evaporated off in vacuo. The residue was chromatographed on silica-gel with EtOAc-n-hexane (1:10 to 1:6, v/v) as eluent to give a syrup which was used for the subsequent reaction without further purification. This syrup was dissolved in CH2Cl2 (10 mL) and added TFA (10 mL). After the solution was stirred for 5 hr at room temp, the solution was evaporated in vacuo. Water was added to the residue and washed with CHCl3. The aqueous layer was neutralized by the addition of sat. NaHCO3 and extracted with CHCl3. The extract was dried over Na2SO4 and evaporated in vacuo to afford 1.03 g (89%) methyl 3-(N,N-dimethylamino)-4-(2-pyrrolidinylmethoxy)benzoate as a gum.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureunder reflux for 41 hr
  3. temperatureAfter cooling
  4. customthe mixture was evaporated off in vacuo
  5. customThe residue was chromatographed on silica-gel with EtOAc-n-hexane (1:10 to 1:6, v/v) as eluent
  6. customto give a syrup which
  7. customwas used for the subsequent reaction without further purification
  8. customthe solution was evaporated in vacuo
  9. additionWater was added to the residue
  10. washwashed with CHCl3
  11. additionThe aqueous layer was neutralized by the addition of sat. NaHCO3
  12. extractionextracted with CHCl3
  13. dry with materialThe extract was dried over Na2SO4
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-02c3c737c57740b4a276052407b3900c
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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