Ammonium Chloride → tert-butyl 4-{2-[methoxy(methyl)amino]-2-oxo-1-(tetrahydro-2H-pyran-4-ylmethyl)ethyl}benzoate

HRID 1881834Notes

Reaction equation

HRID 1881834 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][N:11]([CH3:28])[C:12](=[O:27])[CH2:13][C:14]1[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=1.I[CH2:30][CH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.[Cl-].[NH4+]>O1CCCC1.CN1CCCN(C)C1=O>[CH3:9][O:10][N:11]([CH3:28])[C:12](=[O:27])[CH:13]([C:14]1[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=1)[CH2:30][CH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 27955074-(Iodomethyl)oxaneHCID 59331582Tert-butyl 4-{2-[methoxy(methyl)amino]-2-oxoethyl}benzoate

Product 1

HCID 59331574tert-butyl 4-{2-[methoxy(methyl)amino]-2-oxo-1-(tetrahydro-2H-pyran-4-ylmethyl)ethyl}benzoateYield 76.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

Lithium diisopropylamide (2M tetrahydrofuran solution, 6.9 mL) was diluted with tetrahydrofuran (20 mL), a solution of tert-butyl 4-{2-[methoxy(methyl)amino]-2-oxoethyl}benzoate (3.70 g) in a mixed solvent of tetrahydrofuran (20 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (12 mL) were added at −78° C., and the mixture was stirred for 1 hr. To the reaction mixture was added a solution of 4-(iodomethyl)tetrahydro-2H-pyran (3.30 g) in tetrahydrofuran m (20 mL) at −78° C. and the mixture was stirred for 3 hr. The mixture was slowly warmed to room temperature, and stirred overnight. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (3.81 g, yield 76%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). MS: 378 (MH+).

Workup

  1. stirringthe mixture was stirred for 3 hr
  2. stirringstirred overnight
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-fc51fa5f4a0f40d689c70d5ebe3abd47
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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