Hydrochloric Acid → tert-Butyl 4-(((6-methoxy-4-oxo-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-7-yl)oxy)methyl)piperidine-1-carboxylate

HRID 1791555Notes

Reaction equation

HRID 1791555 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:20])[N:7]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=[N:9]2)=[CH:4][C:3]=1[O:21][CH3:22].CC1C=CC(S(O[CH2:34][CH:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)(=O)=O)=CC=1.Cl>CN(C=O)C>[CH3:22][O:21][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:34][CH:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:45])([CH3:47])[CH3:46])=[O:42])[CH2:37][CH2:36]1)[N:9]=[CH:8][N:7]([CH2:12][O:13][C:14](=[O:19])[C:15]([CH3:16])([CH3:17])[CH3:18])[C:6]2=[O:20]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidineHCID 10804576(7-Hydroxy-6-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate

Product 1

HCID 11733854tert-Butyl 4-(((6-methoxy-4-oxo-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-7-yl)oxy)methyl)piperidine-1-carboxylateYield 78.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (6.12 g, 20 mmol) potassium carbonate (5.52 g, 40 mmol) in DMF (60 ml) was stirred at ambient temperature for 30 minutes. 4-(4-Methylphenylsulphonyloxymethyl)-1-tert-butyloxycarbonylpiperidine (8.86 g, 24 mmol), (prepared as described for the starting material in Example 10), was added and the mixture was stirred at 100° C. for 2 hours. After cooling, the mixture was poured onto water/ice (400 ml, 1/1) containing 2M hydrochloric acid (10 ml). The precipitate was collected by filtration, washed with water and dried under vacuum over phophorus pentoxide. The solid was triturated in a mixture of ether/pentane (1/1), collected by filtration and dried to give 6-methoxy-3-((pivaloyloxy)methyl)-7-((1-tert-butyloxycarbonylpiperidin-4-yl)methoxy)-3,4-dihydroquinazolin-4-one (7.9 g, 78.5%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at 100° C. for 2 hours
  3. temperatureAfter cooling
  4. additionthe mixture was poured onto water/ice (400 ml, 1/1)
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with water
  7. customdried under vacuum over phophorus pentoxide
  8. customThe solid was triturated in a mixture of ether/pentane (1/1)
  9. filtrationcollected by filtration
  10. customdried

Sources & evidence

ORD record
ord-8ccda9cb1d66403782b1f8739af8d082
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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