Carbon Dioxide → 2-(tert-Butoxycarbonylamino)-3-fluoro-benzoic acid

HRID 2250273Notes

Reaction equation

HRID 2250273 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].C([Li])(C)(C)C.[C:21](=[O:23])=[O:22]>O1CCCC1.CCCCC>[C:11]([O:10][C:9]([NH:8][C:3]1[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=1[C:21]([OH:23])=[O:22])=[O:15])([CH3:12])([CH3:14])[CH3:13]

Participants

6

Reactant 3

HCID 280Carbon DioxideHCID 4935500Tert-butyl 2-fluorophenylcarbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 112882942-(tert-Butoxycarbonylamino)-3-fluoro-benzoic acid

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl 2-fluorophenylcarbamate (44.0 g, 208 mmol) in tetrahydrofuran (660 mL) at −78° C. was added tert-butyllithium in pentane (1.7 M, 306 mL, 2.5 equivx) dropwise. After addition was complete, the reaction was stirred at −78° C. for 30 min. The solution was allowed to gradually reach −20° C. before being recooled to −78° C. and transferred via canula to a slurry of carbon dioxide (excess) and tetrahydrofuran (500 mL). The solution was allowed to slowly warm to room temperature. The reaction mixture was concentrated to remove most of the tetrahydrofuran, and poured into a sep funnel containing water and diethyl ether. The layers were separated, and the aqueous extracted with diethyl ether twice more. The ethereals were discarded. The aqueous was acidified with 5% citric acid, extracted with diethyl ether (3×). The ethereal was dried over magnesium sulfate, and concentrated to give a light yellow solid which was recrystallized from hot toluene to give 37.1 g (70%) as a faint yellow solid. 1H-NMR (CDCl3, 500 MHz) δ 1.50 (s, 9H), 6.25 (bs, 1H), 7.18 (ddd, J=7.9, 7.9, 4.9, 1H), 7.33 (dd, J=9.5, 9.2, 1H), 7.79 (d, J=7.9, 1H), 7.94 (s, 1H). Mass spec.: 278.21 (MNa)+.

Workup

  1. additionAfter addition
  2. customwas allowed to gradually reach −20° C.
  3. custombefore being recooled to −78° C.
  4. temperatureto slowly warm to room temperature
  5. concentrationThe reaction mixture was concentrated
  6. customto remove most of the tetrahydrofuran
  7. additionpoured into a sep funnel
  8. additioncontaining water and diethyl ether
  9. customThe layers were separated
  10. extractionthe aqueous extracted with diethyl ether twice more
  11. extractionextracted with diethyl ether (3×)
  12. dry with materialThe ethereal was dried over magnesium sulfate
  13. concentrationconcentrated
  14. customto give a light yellow solid which
  15. customwas recrystallized from hot toluene
  16. customto give 37.1 g (70%) as a faint yellow solid

Sources & evidence

ORD record
ord-f31914ef9379460595baef632dae8a9d
Source dataset
uspto-grants-2008_01
Patent number
US07314883B2

Reaction notes

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