Trifluoroacetic acid → HCID 136104957, compound

HRID 2062286Notes

Reaction equation

HRID 2062286 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([CH3:24])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[OH:31])[N:15]=2)[CH2:10][CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([CH3:24])=[CH:21][CH:22]=3)[N:17]=[C:16]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[OH:31])[N:15]=2)[CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136121342HCID 136121342, compound

Product 1

HCID 136104957HCID 136104957, compoundYield 102.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate (55.7 g, 128 mmol) was dissolved in dichloromethane (200 mL) and trifluoroacetic acid (215 ml) was slowly added (careful: immediate gas evolution!). The resulting solution was stirred overnight at room temperature under a nitrogen atmosphere and evaporated to dryness. To the residue were added equal amounts of water and dichloromethane (300 mL). The obtained emulsion was basified to pH 9 with 33% aq. NaOH. The emulsion was cleared by the addition of methanol, and the layers were separated. The aqueous layer was extracted with dichloromethane (200 mL), and the combined organic extracts were dried over sodium sulfate, filtered, and evaporated to dryness to yield crude 2-(4-(4-aminopiperidin-1-yl)-7-methylquinazolin-2-yl)phenol. The crude material was purified by column chromatography (SiO2, 2% methanol in dichloromethane) to yield 2-(4-(4-aminopiperidin-1-yl)-7-methylquinazolin-2-yl)phenol (44 g, 97%) as a yellow solid. 1H-NMR (300 MHz, CDCl3): δ 8.52 (dd, J=2.1, 8.1 Hz, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.62 (s, 1H), 7.37 (dt, J=1.5, 7.2 Hz, 1H), 7.22 (dd, J=1.5, 9.0 Hz, 1H), 7.04 (dd, J=1.2, 6.9 Hz, 1H), 6.92 (dt, J=1.2, 7.2 Hz, 1H), 4.49-4.39 (m, 2H), 3.34 (dt, J=2.4, 12.2 Hz, 2H), 3.12-3.02 (m, 1H), 2.54 (s, 3H), 2.09-2.00 (m, 2H), 1.68-1.55 (m, 2H), 1.40-1.25 (m, 2H) ppm.

Workup

  1. customevaporated to dryness
  2. additionTo the residue were added equal amounts of water and dichloromethane (300 mL)
  3. additionThe emulsion was cleared by the addition of methanol
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with dichloromethane (200 mL)
  6. dry with materialthe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customto yield crude 2-(4-(4-aminopiperidin-1-yl)-7-methylquinazolin-2-yl)phenol
  10. customThe crude material was purified by column chromatography (SiO2, 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-c948812e818146ee82698c667d97bfb7
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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