N-Methoxy-N-methylacetamide → HCID 23589043, compound

HRID 489720Notes

Reaction equation

HRID 489720 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=1[CH3:15])([CH3:4])([CH3:3])[CH3:2].C([Li])(CC)C.CON(C)[C:25](=[O:27])[CH3:26]>O1CCCC1>[C:1]([O:5][C:6](=[O:16])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[C:9]=1[CH2:15][C:25](=[O:27])[CH3:26])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 537505N-Methoxy-N-methylacetamideHCID 4935482tert-Butyl (3-chloro-2-methylphenyl)carbamateHCID 178418400CID 53628100

Product 1

HCID 23589043HCID 23589043, compoundYield 88.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a cold solution of (3-Chloro-2-methyl-phenyl)-carbamic acid tert-butyl ester (5.0 g, 20.7 mmol) in anhydrous tetrahydrofuran (100 ml) at −40° C. under N2, was added a solution of s-butyl lithium (40 ml, 52 mmol, 1.3 M in cyclohexane) dropwise and maintained the reaction temperature below −30° C. To the bright yellow solution at −50° C. was added a solution of N-methoxy N-methylacetamide (2.33 g, 22.6 mmol) in anhydrous tetrahydrofuran (40 ml) dropwise and maintained the reaction temperature between −50° C. to −40° C. The mixture was allowed to warm to −10° C. over a period of 35 minutes and was then partitioned between diethyl ether and 0.3 N hydrochloric acid solution. The organic extract was washed with water and brine, dried (anhydrous sodium sulfate), and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel eluting with 20% ethyl acetate in hexane to give crude [3-Chloro-2-(2-oxo-propyl)-phenyl]-carbamic acid tert-butyl ester (5.21 g) as a colorless oil.

Workup

  1. temperaturemaintained the reaction temperature below −30° C
  2. temperaturemaintained the reaction temperature between −50° C. to −40° C
  3. customwas then partitioned between diethyl ether and 0.3 N hydrochloric acid solution
  4. extractionThe organic extract
  5. washwas washed with water and brine
  6. dry with materialdried (anhydrous sodium sulfate)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography over silica gel eluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-bae8508744e9492c9890a54526de86e2
Source dataset
uspto-grants-2005_12
Patent number
US06979696B2

Reaction notes

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