2-Chloroacetamidine monohydrochloride → 2-(chloromethyl)-6,6-dimethyl-1,5,7,8-tetrahydroquinazolin-4-one

HRID 241020Notes

Reaction equation

HRID 241020 reaction equation
[CH3:1][C:2]1([CH3:13])[CH2:7][CH:6]([C:8]([O:10]C)=O)[C:5](=O)[CH2:4][CH2:3]1.Cl.[Cl:15][CH2:16][C:17](=[NH:19])[NH2:18].C[O-].[Na+]>CO>[Cl:15][CH2:16][C:17]1[N:19]=[C:8]([OH:10])[C:6]2[CH2:7][C:2]([CH3:1])([CH3:13])[CH2:3][CH2:4][C:5]=2[N:18]=1

Participants

5

Reactant 3

HCID 27769572-Chloroacetamidine monohydrochlorideHCID 10942334Sodium MethoxideHCID 12441545Methyl 5,5-dimethyl-2-oxocyclohexane-1-carboxylate

Product 1

HCID 1784239482-(chloromethyl)-6,6-dimethyl-1,5,7,8-tetrahydroquinazolin-4-oneYield 57%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of methyl 5,5-dimethyl-2-oxocyclohexanecarboxylate (6.0 g, 33 mmol) and 2-chloroacetimidamide hydrochloride (4.6 g, 36 mmol) in methanol (30 mL) was added sodium methoxide (4.4 M in MeOH, 9.0 mL, 40 mmol). The reaction mixture was stirred at ambient temperature for three hours and then concentrated. The resulting residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated. Purification by silica gel chromatography provided 2-(chloromethyl)-6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-ol (4.2 g, 57% yield) as a white solid. MS (ES) for C11H15ClN2O: 227 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resulting residue was partitioned between ethyl acetate and aqueous sodium bicarbonate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-76e15e58c8db43899aa2f43f1eee14fe
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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