Dimethylformamide → (4-Formyl-2,6-dimethyl-phenyl)-carbamic acid ethyl ester

HRID 1820112Notes

Reaction equation

HRID 1820112 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[NH:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9](Br)=[CH:8][C:7]=1[CH3:14])[CH3:2].C([Mg]Cl)(C)C.C([Li])(C)(C)C.CN(C)[CH:28]=[O:29]>O1CCCC1.C(O)(=O)C>[CH2:1]([O:3][C:4](=[O:15])[NH:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH:28]=[O:29])=[CH:8][C:7]=1[CH3:14])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11644748(4-Bromo-2,6-dimethyl-phenyl)-carbamic acid ethyl esterHCID 178418306HCID 178418306, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86229075(4-Formyl-2,6-dimethyl-phenyl)-carbamic acid ethyl esterYield 73%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To (4-bromo-2,6-dimethyl-phenyl)-carbamic acid ethyl ester (1t, 1.0 g) dissolved in dry tetrahydrofuran (25 mL) under argon was added isopropylmagnesium chloride (2 M in tetrahydrofuran, 1.9 mL) over 5 minutes and then stirred for 30 minutes. The reaction mixture was cooled to −78° C. and tert-butyllithium (1.7 M in heptane, 4.5 mL) was added dropwise while keeping the internal temperature below −65° C. The temperature of the reaction was raised to −10° C. after complete addition, and then cooled to −78° C. again followed by addition of N,N-dimethylformamide (0.6 mL). The reaction was stirred for 30 minutes at −78° C., 30 minutes at 25° C. and then poured onto crushed ice mixed with acetic acid (25 mL). The mixture was stirred for 30 minutes, extracted with ethyl acetate (3×100 mL), dried over magnesium sulfate, and concentrated in vacuo. The crude product was subjected to flash chromatography to furnish 0.60 g (73% yield) of the title compound as a white solid. LC-MS (m/z) 222 (MH+); tR=2.14, (UV, ELSD) 86%, 99%. 1H NMR (500 MHz, CDCl3): 1.30 (t, 3H), 2.34 (s, 6H), 4.21 (q, 2H), 6.28 (b, 1H), 7.59 (s, 2H), 9.92 (s, 1H).

Workup

  1. customthe internal temperature below −65° C
  2. temperatureThe temperature of the reaction was raised to −10° C.
  3. additionafter complete addition
  4. temperaturecooled to −78° C.
  5. stirringThe reaction was stirred for 30 minutes at −78° C., 30 minutes at 25° C.
  6. additionpoured
  7. customonto crushed ice
  8. stirringThe mixture was stirred for 30 minutes
  9. extractionextracted with ethyl acetate (3×100 mL)
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-39cbde84e41e45289f8f62acc2c00a28
Source dataset
uspto-grants-2009_10
Patent number
US07601870B2

Reaction notes

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