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

HRID 238098Notes

Reaction equation

HRID 238098 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH:20][C:21]1[CH:30]=[C:29]2[C:24]([C:25](=[O:39])[N:26]([CH2:31][O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[CH:27]=[N:28]2)=[CH:23][C:22]=1[O:40][CH3:41].[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([CH2:55]O)[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:44])[CH3:43].N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][CH:52]([CH2:55][O:20][C:21]2[CH:30]=[C:29]3[C:24]([C:25](=[O:39])[N:26]([CH2:31][O:32][C:33](=[O:38])[C:34]([CH3:35])([CH3:36])[CH3:37])[CH:27]=[N:28]3)=[CH:23][C:22]=2[O:40][CH3:41])[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:43])[CH3:44]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 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 9,213.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Triphenylphosphine (1.7 g, 6.5 mmol) was added under nitrogen to a suspension of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (1.53 g, 5 mmol) in methylene chloride (20 ml), followed by the addition of 1-(tert-butoxycarbonyl)-4-(hydroxymethyl)piperidine (1.29 g, 6 mmol), (prepared as described for the starting material in Example 1), and by a solution of diethyl azodicarboxylate (1.13 g, 6.5 mmol) in methylene chloride (5 ml). After stirring for 30 minutes at ambient temperature, the reaction mixture was poured onto a column of silica and was eluted with ethyl acetate/petroleum ether (1/1 followed by 6/5, 6/4 and 7/3). Evaporation of the fractions containing the expected product led to an oil that crystallised following trituration with pentane. The solid was collected by filtration and dried under vacuum to give 7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (232 g, 92%).

Workup

  1. custom(prepared
  2. additionthe reaction mixture was poured onto a column of silica
  3. washwas eluted with ethyl acetate/petroleum ether (1/1 followed by 6/5, 6/4 and 7/3)
  4. customEvaporation of the fractions
  5. additioncontaining the expected product
  6. customcrystallised
  7. filtrationThe solid was collected by filtration
  8. customdried under vacuum

Sources & evidence

ORD record
ord-75461cae9c464d279098f9b736e94df8
Source dataset
uspto-grants-2014_02
Patent number
US08642608B2

Reaction notes

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