Iodine → tert-butyl [(1S)-2-(4-ethylphenyl)-1-methyl-2-oxoethyl]carbamate

HRID 1098780Notes

Reaction equation

HRID 1098780 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH3:10])=[CH:5][CH:4]=1.II.[C:13]([O:17][C:18]([NH:20][C@H:21]([C:23](N(OC)C)=[O:24])[CH3:22])=[O:19])([CH3:16])([CH3:15])[CH3:14]>C1COCC1>[CH2:9]([C:6]1[CH:7]=[CH:8][C:3]([C:23](=[O:24])[C@@H:21]([NH:20][C:18](=[O:19])[O:17][C:13]([CH3:14])([CH3:15])[CH3:16])[CH3:22])=[CH:4][CH:5]=1)[CH3:10]

Participants

6

Reactant 4

HCID 807IodineHCID 153131-Bromo-4-ethylbenzeneHCID 5462224MagnesiumHCID 11806530(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate

Product 1

HCID 59339635tert-butyl [(1S)-2-(4-ethylphenyl)-1-methyl-2-oxoethyl]carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred suspension of magnesium turnings (243 mg, 10 mmol) in dry THF (10 ml) was added a solution of 1-bromo-4-ethylbenzene (1.85 g, 10 mmol) in dry THF (10 ml), followed by a small crystal of iodine. The reaction mixture was heated with reflux for 4 h, then cooled to r.t. A solution of N2-(tert-butoxycarbonyl)-N-methoxy-N-methyl-L-alaninamide (464 mg, 2 mmol) in dry THF (15 ml) was added dropwise, and the stirring was continued for 5 h at r.t. Then the reaction mixture was quenched with sat. aqueous NH4Cl (25 ml) stirred for 30 min, and the layers were separated. The aqueous layer extracted with ethyl acetate (50 ml). The combined organic layers were dried with Na2SO4, and the solvent was removed under reduced pressure to give the subtitle compound as colourless oil, 718 mg, 70% purity (as determined by NMR). Used in the next step without further purification.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperaturewith reflux for 4 h
  3. customThen the reaction mixture was quenched with sat. aqueous NH4Cl (25 ml)
  4. customthe layers were separated
  5. extractionThe aqueous layer extracted with ethyl acetate (50 ml)
  6. dry with materialThe combined organic layers were dried with Na2SO4
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-c219b7da1f564097871fbc8e5f405306
Source dataset
uspto-grants-2012_03
Patent number
US08143290B2

Reaction notes

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