N-Methoxy-N-methylacetamide → HCID 18455601, compound

HRID 1966315Notes

Reaction equation

HRID 1966315 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH:17]([CH3:19])[O:16][CH:15]([CH3:20])[CH2:14]2)=[C:9]([CH:21]2[O:25]CCO2)[CH:8]=1.CON(C)[C:29](=[O:31])[CH3:30]>C1COCC1>[C:29]([C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:14][CH:15]([CH3:20])[O:16][CH:17]([CH3:19])[CH2:18]2)=[C:9]([CH:8]=1)[CH:21]=[O:25])(=[O:31])[CH3:30]

Participants

5

Reactant 3

HCID 537505N-Methoxy-N-methylacetamideHCID 18455590HCID 18455590, compoundHCID 178418306HCID 178418306, compound2×

Product 1

HCID 18455601HCID 18455601, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

t-Butyl lithium in hexanes (3.8 ml of a 1.7 M solution, 14.5 mmol) is added to THF at −78° C. in a flame dried round-bottomed flask. 4-[4-Bromo-2-(1,3-dioxolan-2-yl)phenyl]-2,6-dimethylmorpholine (from Step 2) (1.0 g, 2.9 mmol) is dissolved in THF (5 mL) and is slowly added to the t-BuLi solution over 7 minutes keeping the temperature below −70° C. The mixture is stirred for 30 minutes and N-methoxy-N-methyl-acetamide (0.34 mL, 3.2 mmol) is slowly added dropwise. The reaction is stirred at −78° C. for 30 minutes and then stored at 0° C. overnight. The reaction is quenched with 1 M HCl (22.5 mL) and then heated at 65° C. for 1 hour. The mixture is basified with 1 M aqueous Na2CO3 and extracted with EtOAc (2×). The combined organic layers are washed with brine, dried (Na2SO4) and concentrated. The resulting residue is adsorbed onto silica gel and purified by silica gel chromatography using 15-20% EtOAc in heptane as the eluent to afford 0.35 g (45%) a clear oil. 1H NMR (400 MHz, CDCl3) δ 10.1, 8.35, 8.12, 7.08, 3.93, 3.25, 2.76, 2.60, 1.25.

Workup

  1. customthe temperature below −70° C
  2. stirringThe reaction is stirred at −78° C. for 30 minutes
  3. waitstored at 0° C. overnight
  4. customThe reaction is quenched with 1 M HCl (22.5 mL)
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-afa5124e951a4f4ebeb4dd1fb781f324
Source dataset
uspto-grants-2013_04
Patent number
US08420646B2

Reaction notes

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