Iodine → (6-Fluoro-2-iodo-3-trifluoromethoxy-phenyl)-carbamic acid ethyl ester

HRID 455975Notes

Reaction equation

HRID 455975 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[NH:5][C:6]1[CH:11]=[C:10]([O:12][C:13]([F:16])([F:15])[F:14])[CH:9]=[CH:8][C:7]=1[F:17])[CH3:2].[Li]C(CC)C.[I:24]I.[NH4+].[Cl-]>C1COCC1>[CH2:1]([O:3][C:4](=[O:18])[NH:5][C:6]1[C:7]([F:17])=[CH:8][CH:9]=[C:10]([O:12][C:13]([F:15])([F:14])[F:16])[C:11]=1[I:24])[CH3:2]

Participants

6

Reactant 4

HCID 807IodineHCID 25517Ammonium ChlorideHCID 46175561(2-Fluoro-5-trifluoromethoxy-phenyl)-carbamic acid ethyl esterHCID 178418400CID 53628100

Product 1

HCID 46175562(6-Fluoro-2-iodo-3-trifluoromethoxy-phenyl)-carbamic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2 (31.34 g, 117.2 mmol) in THF (180 mL) at −78° C. is added sec-BuLi (1.4 M in cyclohexane, 200 mL, 280 mmol) dropwise over a 1 h period. After 20 min, a solution of I2 (44.6 g, 175.8 mmol) in THF (150 mL) is added dropwise over a 30 min period. This mixture is then stirred at −78° C. for 30 min. Saturated NH4Cl is added, and the cooling bath is removed. The reaction mixture is partitioned between H2O and EtOAc. The two layers are separated, and the organic layer is washed with 10% Na2SO3, H2O, and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue is suspended in DCM (50 mL), and heptane (300 mL) is added. The white powder 3 (18.1 g, 39%) from the resulting suspension is collected by suction filtration and air-dried. The filtrate is concentrated in vacuo, and the residue is suspended in heptane (200 mL). Another batch of 3 (3.8 g, 8%) is collected by suction filtration and air-dried. Additional product can be obtained by purifying the filtrate via silica gel chromatography. 1H NMR (CDCl3) δ 7.30-17.10 (m, 2H), 6.16 (br s, 1H), 4.26 (q, J=7.1 Hz, 2H), 1.32 (t, J=7.1 Hz, 3H); 19F NMR (CDCl3) δ−56.90 (s, 3F), −114.35 (d, J=8.5 Hz, 1F); MS 394 (M+1, 100%), 374, 364, 321, 267.

Workup

  1. customthe cooling bath is removed
  2. customThe reaction mixture is partitioned between H2O and EtOAc
  3. customThe two layers are separated
  4. washthe organic layer is washed with 10% Na2SO3, H2O, and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionheptane (300 mL) is added
  9. filtrationThe white powder 3 (18.1 g, 39%) from the resulting suspension is collected by suction filtration
  10. customair-dried
  11. concentrationThe filtrate is concentrated in vacuo
  12. filtrationAnother batch of 3 (3.8 g, 8%) is collected by suction filtration
  13. customair-dried
  14. customAdditional product can be obtained
  15. customby purifying the filtrate via silica gel chromatography

Sources & evidence

ORD record
ord-7a9c66a263d44f4f85fdd7d4f8e2b6cd
Source dataset
uspto-grants-2013_07
Patent number
US08497379B2

Reaction notes

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