Trifluoroacetic acid → 2-(4-(4-Aminopiperidin-1-yl)-7-methylquinazolin-2-yl)-3-fluorophenol

HRID 2062295Notes

Reaction equation

HRID 2062295 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[C:9]1[N:18]=[C:17]([N:19]2[CH2:24][CH2:23][CH:22]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH2:20]2)[C:16]2[C:11](=[CH:12][C:13]([CH3:33])=[CH:14][CH:15]=2)[N:10]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:25][CH:22]1[CH2:21][CH2:20][N:19]([C:17]2[C:16]3[C:11](=[CH:12][C:13]([CH3:33])=[CH:14][CH:15]=3)[N:10]=[C:9]([C:3]3[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=3[OH:8])[N:18]=2)[CH2:24][CH2:23]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136121470Tert-butyl 1-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate

Product 1

HCID 1361213392-(4-(4-Aminopiperidin-1-yl)-7-methylquinazolin-2-yl)-3-fluorophenolYield 92.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 1-(2-(2-fluoro-6-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-4-ylcarbamate (1.05 g, 2.3 mmol) in 20 ml CH2Cl2 was slowly added TFA (5 mL). The reaction was stirred for one hour before it was evaporated to dryness. To the residue was added CH2Cl2, and the reaction was neutralized using an aqueous 1 M NaOH solution. The aqueous layer was extracted twice with CH2Cl2, and the combined organic layers were dried over MgSO4, filtered, and concentrated to obtain 2-(4-(4-aminopiperidin-1-yl)-7-methylquinazolin-2-yl)-3-fluorophenol (0.75 g, 92%). LC/MS: m/z 353.3 (M+H)+ at 1.35 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customwas evaporated to dryness
  2. additionTo the residue was added CH2Cl2
  3. extractionThe aqueous layer was extracted twice with CH2Cl2
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5e76527ebdda4d73965358bdd70c610b
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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