Toluene → Tert-butyl 2-fluoro-6-formylphenylcarbamate

HRID 501972Notes

Reaction equation

HRID 501972 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].C1(C)C=CC=CC=1.C([Li])(C)(C)C.CN(C)[CH:30]=[O:31]>O.C(OCC)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:30]=[O:31])[C:3]=1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 1140TolueneHCID 6228DimethylformamideHCID 4935500Tert-butyl 2-fluorophenylcarbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 11506970Tert-butyl 2-fluoro-6-formylphenylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

tert-Butyl 2-fluorophenylcarbamate (42.7 g, 202 mmol) was concentrated from toluene in vacuo (3×) to remove any traces of water. The resulting residue was dissolved in tetrahydrofuran (600 mL), and cooled to −78° C. To this was added tert-butyllithium (1.7 M in pentane, 285 mL, 485 mmol) in dropwise fashion. After addition was complete, the reaction was stirred at −78° C. for 30 minutes. The solution was allowed to gradually warm to −20° C. before re-cooling to −78° C. To this was added dimethylformamide (46.9 mL, 606 mmol). The reaction was allowed to gradually warm to room temperature overnight. The reaction was poured into a separatory funnel containing diethyl ether and water. The organics were washed with water (3×) and concentrated. The combined aqueous washes were neutralized with 1 M potassium bisulfate and extracted with diethyl ether. The ethereal layers were combined with the other organics, washed with water, then brine, dried over magnesium sulfate, and concentrated to give 48.1 g (100%) as a yellow oil which was used without further purification. 1H-NMR (CDCl3, 500 MHz) δ 1.50 (s, 9H), 7.27 (m, 1H), 7.35 (m, 1H), 7.56 (d, J=7.6 Hz, 1H), 7.85 (bs, 1H), 9.99 (d, J=1.2 Hz, 1H). Mass spec.: 262.16 (MNa)+.

Workup

  1. customto remove any traces of water
  2. dissolutionThe resulting residue was dissolved in tetrahydrofuran (600 mL)
  3. additionAfter addition
  4. temperatureto gradually warm to −20° C.
  5. temperaturebefore re-cooling to −78° C
  6. temperatureto gradually warm to room temperature overnight
  7. additionThe reaction was poured into a separatory funnel
  8. washThe organics were washed with water (3×)
  9. concentrationconcentrated
  10. extractionextracted with diethyl ether
  11. washwashed with water
  12. dry with materialbrine, dried over magnesium sulfate
  13. concentrationconcentrated
  14. customto give 48.1 g (100%) as a yellow oil which
  15. customwas used without further purification

Sources & evidence

ORD record
ord-2f45b0cecbff4879837f2e2fe92418b7
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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