Methyl iodide → HCID 67512835, compound

HRID 1508465Notes

Reaction equation

HRID 1508465 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.CN1C(=O)N(C)CCC1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH:27]([CH3:35])[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:22][CH:21]=1.CI>C1COCC1>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([CH3:2])([CH3:35])[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 67513696HCID 67513696, compound

Product 1

HCID 67512835HCID 67512835, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

An oven dried flask was charged with THF (40 mL) under nitrogen and cooled to −78° C. and 2M LDA in THF (7.19 mL, 14.38 mmol) was added dropwise followed by DMPU (8 mL, 5.75 mmol). Tert-butyl 3-(4-methoxyphenyl)-2-methylpropanoate (1.44 g, 5.75 mmol) was added by cannula in THF (4×5 mL), and the reaction was stirred at −78° C. for 1 hr. Methyl iodide (1.079 mL, 17.26 mmol) was added dropwise, and the reaction was stirred 30 minutes at −78° C. and then warmed to room temperature for 1 hr. The reaction was quenched with water (40 mL) and extracted with ethyl acetate (50 mL). The organic layer was washed with 1N HCl (2×30 mL) and brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (0 to 60% ethyl acetate/hexanes) afforded tert-butyl 3-(4-methoxyphenyl)-2,2-dimethylpropanoate. 1H NMR (CDCl3, 500 MHz) δ 7.07 (d, J=8.5 Hz, 2H), 6.79 (d, J=8.7 Hz, 2H), 3.78 (s, 3H), 2.76 (s, 2H), 1.43 (s, 9H), 1.11 (s, 6H).

Workup

  1. customAn oven dried flask
  2. additionwas charged with THF (40 mL) under nitrogen
  3. stirringthe reaction was stirred 30 minutes at −78° C.
  4. temperaturewarmed to room temperature for 1 hr
  5. customThe reaction was quenched with water (40 mL)
  6. extractionextracted with ethyl acetate (50 mL)
  7. washThe organic layer was washed with 1N HCl (2×30 mL) and brine (2×30 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the residue by flash chromatography on silica gel (0 to 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-edcc933883f44a44b9ea39839cb73078
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

Loading…