Triphenylphosphine → 7-{[1-(Tert-butoxycarbonyl)-piperidin-4-yl]oxy}-4-chloro-6-methoxyquinazoline

HRID 1668694Notes

Reaction equation

HRID 1668694 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:14])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][CH:44](O)[CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][CH:44]([O:14][C:8]2[CH:7]=[C:6]3[C:11]([C:2]([Cl:1])=[N:3][CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])[CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:35])[CH3:36]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 1357422514-Chloro-6-methoxyquinazolin-7-ol

Product 1

HCID 596829067-{[1-(Tert-butoxycarbonyl)-piperidin-4-yl]oxy}-4-chloro-6-methoxyquinazolineYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 4-chloro-7-hydroxy-6-methoxyquinazoline (11.5 g), prepared as described in Example 1, in dichloromethane (250 ml) was treated with triphenylphosphine (21.5 g), 1-(tert-butoxycarbonyl)-4-hydroxypiperidine (13.2 g) and di-tert-butyl azodicarboxylate (19 g) and the mixture stirred at ambient temperature overnight. The crude reaction mixture was concentrated to a third and loaded onto a silica column and eluted using ethyl acetate/petroleum ether (35/65) as solvent. The relevant fractions were combined and evaporated under vacuum to give 7-{[1-(tert-butoxycarbonyl)-piperidin-4-yl]oxy}-4-chloro-6-methoxyquinazoline as a white solid (20 g).

Workup

  1. customprepared
  2. customThe crude reaction mixture
  3. concentrationwas concentrated to a third
  4. washeluted
  5. customevaporated under vacuum

Sources & evidence

ORD record
ord-5ad5cbda2eda47e8aec5b7d76e9ae716
Source dataset
uspto-grants-2011_08
Patent number
US07989460B2

Reaction notes

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