Dimethylformamide → tert-Butyl 2-(4-Formylphenyl)-2-hydroxyethyl(methyl)carbamate

HRID 23716Notes

Reaction equation

HRID 23716 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:19])[CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1.CN(C)CCN(C)C.C[Mg+].[Br-].[Li]CCCC.CN([CH:39]=[O:40])C.[Cl-].[NH4+]>C1COCC1.CCCCCC.CCOCC>[CH:39]([C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:19])[CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1)=[O:40]

Participants

10

Reactant 6

HCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 22574334tert-butyl N-[2-(4-bromophenyl)-2-hydroxyethyl]-N-methylcarbamateHCID 178418339ButyllithiumHCID 178418689HCID 178418689, compound

Product 1

HCID 22574298tert-Butyl 2-(4-Formylphenyl)-2-hydroxyethyl(methyl)carbamateYield 68.6%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

tert-Butyl 2-(4-bromophenyl)-2-hydroxyethyl(methyl)carbamate (36.7 g, 111.2 mmol) was dissolved in dry THF (600 ml) under N2 and tetramethyl ethylenediamine (42.2 ml, 32.5 g, 280.1 mmol) was added. The stirred mixture was cooled in an ice bath and a 3M ether solution of MeMgBr (46.4 ml, 139.3 mmol). After stirring for 1 hr a 1.6M hexane solution of nBuLi (150 ml, 240 mmol) was added and stirred for an additional 1 hr at which time dry DMF (50 ml, 47.2 g, 647 mmol) was added. After 1 hr a satd. solution (100 ml) of ammonium chloride was added. Most of the organic solvent was evaporated and the residual mass was extracted with ethyl acetate (3×500 ml), washed with water (300 ml) and brine (100 ml) then dried over magnesium sulfate. Filtration and evaporation gave a viscous oil that was chromatographed over silica gel (500 g). Elution with 25-40% ethyl acetate-hexane gave the product as a pale yellow gum (21.3 g) which very slowly crystallized to a yellow solid.

Workup

  1. temperatureThe stirred mixture was cooled in an ice bath
  2. additionwas added
  3. additionwas added
  4. customMost of the organic solvent was evaporated
  5. extractionthe residual mass was extracted with ethyl acetate (3×500 ml)
  6. washwashed with water (300 ml) and brine (100 ml)
  7. dry with materialthen dried over magnesium sulfate
  8. filtrationFiltration and evaporation
  9. customgave a viscous oil that
  10. customwas chromatographed over silica gel (500 g)
  11. washElution with 25-40% ethyl acetate-hexane

Sources & evidence

ORD record
ord-ae2eadb21b324308b278fb502597ee8c
Source dataset
uspto-grants-2005_02
Patent number
US06852731B2

Reaction notes

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