Tetrahydrofuran → 5-Hydroxy-7-methoxy-3-pivaloyloxymethyl-quinazolin-4-one

HRID 631350Notes

Reaction equation

HRID 631350 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]2[C:3]=1[C:4](=[O:14])[NH:5][CH:6]=[N:7]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[C:30]([O:36][CH2:37]Cl)(=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32]>CN(C=O)C>[C:30]([O:36][CH2:37][N:5]1[C:4](=[O:14])[C:3]2[C:8](=[CH:9][C:10]([O:12][CH3:13])=[CH:11][C:2]=2[OH:1])[N:7]=[CH:6]1)(=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 87885Chloromethyl pivalateHCID 2733832Lithium HexamethyldisilazideHCID 1355106955-hydroxy-7-methoxyquinazolin-4(3H)-one

Product 1

HCID 119745575-Hydroxy-7-methoxy-3-pivaloyloxymethyl-quinazolin-4-oneYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 5-hydroxy-7-methoxyquinazolin-4(3H)-one (4.395 g, 22.9 mmol) in DMF (50 mL) at 0° C. was added 1.0 M solution of lithium bis(trimethylsilyl)amide in THF (55 mL, 55 mmol). After it was stirred at room temperature for 1 hour, it was cooled again with an ice-water bath and to it was added chloromethyl pivalate (4.14 g, 27.5 mmol). After it was stirred at room temperature for another hour, it was quenched with a solution of AcOH (10 mL) in water (150 mL) and extracted with CH2Cl2. Extracts were dried over MgSO4 and concentrated to afford the (5-hydroxy-7-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate solid (5.674 g, 81%). 1H NMR (300 MHz, CDCl3) δ 11.36 (s, 1H), 8.16 (s, 1H), 6.69 (d, 1H), 6.51 (d, 1H), 5.88 (s, 2H), 3.89 (s, 3H), 1.21 (s, 9H); LC-MS (ESI) m/z 307 (M+H)+.

Workup

  1. temperatureit was cooled again with an ice-water bath and to it
  2. stirringAfter it was stirred at room temperature for another hour
  3. customit was quenched with a solution of AcOH (10 mL) in water (150 mL)
  4. extractionextracted with CH2Cl2
  5. dry with materialExtracts were dried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-7a2d1f02ea764a8f87075e0acd9ca475
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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