tert-Butanol → Carbamic acid, N-(3-bromo-5-chloro-2-fluorophenyl)-, 1,1-dimethylethyl ester

HRID 535719Notes

Reaction equation

HRID 535719 reaction equation
[Br:1][C:2]1[C:3]([F:12])=[C:4]([CH:8]=[C:9]([Cl:11])[CH:10]=1)C(O)=O.CC[N:15]([CH:19](C)C)C(C)C.C1C=CC([O:28]P(OC2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1.[C:41]([OH:45])([CH3:44])([CH3:43])[CH3:42]>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:3]([F:12])=[C:4]([NH:15][C:19](=[O:28])[O:45][C:41]([CH3:44])([CH3:43])[CH3:42])[CH:8]=[C:9]([Cl:11])[CH:10]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 123414Diphenylphosphoryl azideHCID 510344623-Bromo-5-chloro-2-fluorobenzoic acid

Product 1

HCID 51034463Carbamic acid, N-(3-bromo-5-chloro-2-fluorophenyl)-, 1,1-dimethylethyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 3-bromo-5-chloro-2-fluorobenzoic acid (3.34 g, 13.2 mmol), DIEA (2.04 g, 15.8 mmol) and diphenyl phosphorazide (DPPA, 4.53 g, 16.5 mmol) in 1:1 dry t-butanol and toluene (35 mL) was heated to and maintained at reflux for 23 hours. The reaction was allowed to cool to room temperature and was then partitioned between CHCl3 (75 mL) and water (75 mL). The organic layer was separated, washed with brine, dried (Na2SO4), and then concentrated under reduced pressure to yield an oily residue. Purification by flash chromatography (SiO2, 0-5% EtOAc in heptane) to yield tert-butyl 3-bromo-5-chloro-2-fluorophenylcarbamate (2.45 g, 7.5 mmol, 57%): LCMS (m/z) not ionized (MH+), tR=1.20 minutes; 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J=5.1 Hz, 1H), 7.16 (m, 1H), 6.72 (br s, 1H), 1.53 (s, 9H).

Workup

  1. temperaturewas heated to and
  2. temperaturemaintained
  3. temperatureat reflux for 23 hours
  4. customwas then partitioned between CHCl3 (75 mL) and water (75 mL)
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customto yield an oily residue
  10. customPurification by flash chromatography (SiO2, 0-5% EtOAc in heptane)

Sources & evidence

ORD record
ord-e50e2957dfec4596aa3605b61bb8ba85
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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