Trifluoroacetic acid → (R)-2-(4-(3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol

HRID 1693009Notes

Reaction equation

HRID 1693009 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:17]=[C:16]([N:18]2[CH2:22][CH2:21][C@@H:20]([NH:23]C(=O)OC(C)(C)C)[CH2:19]2)[C:15]2[C:10](=[CH:11][C:12]([CH3:31])=[CH:13][CH:14]=2)[N:9]=1.FC(F)(F)C(O)=O>ClCCl>[NH2:23][C@@H:20]1[CH2:21][CH2:22][N:18]([C:16]2[C:15]3[C:10](=[CH:11][C:12]([CH3:31])=[CH:13][CH:14]=3)[N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[OH:1])[N:17]=2)[CH2:19]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136121326tert-butyl(R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

Product 1

HCID 136121376(R)-2-(4-(3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenolYield 95.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (15.1 g, 36 mmol) was treated with trifluoroacetic acid (50 mL) in dichloromethane (100 mL) at room temperature for about three hours. The solution was evaporated to dryness and the residue was stripped with toluene (100 mL). 10% aq. sodium carbonate solution (300 mL), CH2Cl2 (400 mL), and methanol (100 mL) [methanol is added because 2-(4-((R)-3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol is not very soluble in pure CH2Cl2] were added to the residue and stirring was continued until all solids were dissolved. The layers were separated and the aqueous layer was extracted with a mixture of CH2Cl2 (400 mL) and methanol (100 mL). The combined organic layers were washed with saturated aqueous NaCl solution (200 mL), dried over sodium sulfate, filtered, and evaporated to dryness to give 2-(4-((R)-3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol (11.0 g, 95%) as a yellow solid with 98+% purity.

Workup

  1. customThe solution was evaporated to dryness
  2. addition10% aq. sodium carbonate solution (300 mL), CH2Cl2 (400 mL), and methanol (100 mL) [methanol is added because 2-(4-((R)-3-aminopyrrolidin-1-yl)-7-methylquinazolin-2-yl)phenol
  3. additionwere added to the residue
  4. dissolutionwere dissolved
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with a mixture of CH2Cl2 (400 mL) and methanol (100 mL)
  7. washThe combined organic layers were washed with saturated aqueous NaCl solution (200 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-593cf905c69943bd99dd6a3710c27a57
Source dataset
uspto-grants-2012_04
Patent number
US08158637B2

Reaction notes

Loading…