Acetic Acid → 7-(2-(1-Methylpiperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one

HRID 454228Notes

Reaction equation

HRID 454228 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][O:9][C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:28])[N:15]([CH2:20][O:21][C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24])[CH:16]=[N:17]3)=[CH:12][C:11]=2[O:29][CH3:30])[CH2:3][CH2:2]1.C=O.[C:33](O)(=O)C.C(O)(=O)C.C(O)(=O)C.C(O)(=O)C.[BH4-].[Na+]>CO.C(Cl)Cl>[CH3:33][N:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][O:9][C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:28])[N:15]([CH2:20][O:21][C:22](=[O:27])[C:23]([CH3:26])([CH3:24])[CH3:25])[CH:16]=[N:17]3)=[CH:12][C:11]=2[O:29][CH3:30])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 117324937-(2-(Piperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-oneHCID 131724855Sodium borohydride triacetate

Product 1

HCID 111128387-(2-(1-Methylpiperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-oneYield 68%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-(2-(piperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (6 g, 14.4 mmol) in methanol (30 ml) and methylene chloride (60 ml) was added 37% aqueous formaldehyde (2.2 ml; 28.9 mmol) followed by acetic acid (990 μl; 17.3 mmol). Sodium borohydride triacetate (4.6 g, 21.6 mmol) was added in portions. After stirring for 1 hour at ambient temperature, the volatiles were removed under vacuum and the residue was partitioned between water (50 ml) and methylene chloride (50 ml). The pH of the aqueous layer was adjusted to 7, washed with water, brine, dried (MgSO4) and evaporated. The solid was triturated with ether, filtered, washed with ether and dried under vacuum to give 7-(2-(1-methylpiperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (4.2 g, 68%).

Workup

  1. customthe volatiles were removed under vacuum
  2. customthe residue was partitioned between water (50 ml) and methylene chloride (50 ml)
  3. washwashed with water, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe solid was triturated with ether
  7. filtrationfiltered
  8. washwashed with ether
  9. customdried under vacuum

Sources & evidence

ORD record
ord-86a203898e0b4a45aa2fd97ee024a6ff
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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