Triphenylphosphine → 7-methoxy-5-(N-methylpiperidin-4-yloxy)-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one

HRID 641717Notes

Reaction equation

HRID 641717 reaction equation
N(C(OC(C)(C)C)=O)=NC([O-])=O.[OH:13][C:14]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]2[C:15]=1[C:16](=[O:34])[N:17]([CH2:26][O:27][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])[CH:18]=[N:19]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH:55]1[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]1>C(Cl)Cl>[CH3:25][O:24][C:22]1[CH:21]=[C:20]2[C:15]([C:16](=[O:34])[N:17]([CH2:26][O:27][C:28](=[O:33])[C:29]([CH3:31])([CH3:30])[CH3:32])[CH:18]=[N:19]2)=[C:14]([O:13][CH:55]2[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]2)[CH:23]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 660484-Piperidinol, 1-methyl-HCID 119745575-Hydroxy-7-methoxy-3-pivaloyloxymethyl-quinazolin-4-oneHCID 86609045Tert-butyl azodicarboxylate

Product 1

HCID 119739027-methoxy-5-(N-methylpiperidin-4-yloxy)-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-oneYield 88.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of di-(tert-butyl azodicarboxylate (1.7 g) in methylene chloride (5 ml) was added to a stirred mixture of 5-hydroxy-7-methoxy-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one (1.5 g), triphenylphosphine (1.9 g), 4-hydroxy-1-methylpiperidine (0.675 g) and methylene chloride (20 ml) which had been cooled to 5° C. The mixture was stirred at ambient temperature for 1 hour. The mixture was evaporated and the residue was purified by column chromatography on silica using a 9:10:1 mixture of methylene chloride, ethyl acetate and a saturated methanolic ammonia solution as eluent. The material so obtained was triturated under diethyl ether. The resultant solid was washed with diethyl ether and dried under vacuum to give 7-methoxy-5-(N-methylpiperidin-4-yloxy)-3-pivaloyloxymethyl-3,4-dihydroquinazolin-4-one (1.75 g); NMR Spectrum: (CDCl3): 1.2 (s, 9H), 2.05 (br s, 41, 2.3 (s, 3H), 2.3-2.42 (m, 2H), 2.7-2.8 (m, 2H), 3.9 (s, 3H), 4.48 (m, 1H), 5.9 (s, 2H), 6.5 (d, 1H), 6.71 (d, 1H), 8.18 (s, 1H).

Workup

  1. customThe mixture was evaporated
  2. customthe residue was purified by column chromatography on silica using
  3. additiona 9:10:1 mixture of methylene chloride, ethyl acetate
  4. customThe material so obtained
  5. customwas triturated under diethyl ether
  6. washThe resultant solid was washed with diethyl ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-4da9ba0d04a741cd85982d96f0fe79a4
Source dataset
uspto-grants-2010_04
Patent number
US07696214B2

Reaction notes

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