Triphenylphosphine → Tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate

HRID 857947Notes

Reaction equation

HRID 857947 reaction equation
CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:29][CH3:30])=[C:25]([OH:28])[CH:26]=2)[N:21]=[CH:20][N:19]=1.O[CH:32]1[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:29][CH3:30])=[C:25]([O:28][CH:32]3[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]3)[CH:26]=2)[N:21]=[CH:20][N:19]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 231324754-Chloro-7-methoxyquinazolin-6-ol

Product 1

HCID 86599788Tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylateYield 97.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Di-tert-butylazodicarboxylate (9.22 g) in methylene chloride (20 ml) was added slowly to a stirred suspension of 4-chloro-6-hydroxy-7-methoxyquinazoline (5.63 g), 4-hydroxy-1-tert-butoxycarbonylpiperidine (8.06 g) and triphenylphosphine (10.5 g) in methylene chloride (100 ml) at 5° C. under an atmosphere of nitrogen. The reaction mixture was allowed to warm to room temperature for 16 hours. The reaction mixture was then evaporated under vacuum and adsorbed onto silica and the product was eluted with isohexane/ethyl acetate/triethylamine (75/24/1 followed by 70/29/1). The fractions containing the desired product were combined and evaporated under vacuum to give tert-butyl 4-[(4-chloro-7-methoxyquinazolin-6-yl)oxy]piperidine-1-carboxylate as a white solid (10.3 g); 1H NMR Spectrum: (DMSO d6) 1.40 (s, 9H), 1.56–1.69 (m, 2H), 1.93–2.04 (m, 2H), 3.20–3.31 (m, 2H), 3.60–3.70 (m, 2H), 4.00 (s, 3H), 4.89 (m, 1H), 7.45 (s, 1H), 7.50 (s, 1H), 8.86 (s, 1H); Mass Spectrum: (M+H)30 394.

Workup

  1. customThe reaction mixture was then evaporated under vacuum
  2. washthe product was eluted with isohexane/ethyl acetate/triethylamine (75/24/1 followed by 70/29/1)
  3. additionThe fractions containing the desired product
  4. customevaporated under vacuum

Sources & evidence

ORD record
ord-3a7b8d68c8fd4f238d6469be95efcfb2
Source dataset
uspto-grants-2006_12
Patent number
US07148230B2

Reaction notes

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