Methyl chloroformate → HCID 59441840, compound

HRID 1014166Notes

Reaction equation

HRID 1014166 reaction equation
CC([N:5]([C:9]1[CH:14]=[CH:13][C:12]([F:15])=[C:11]([F:16])[CH:10]=1)[C:6](=[O:8])[O-:7])(C)C.[Li][C:18]([CH3:21])([CH3:20])[CH3:19].CCCCC.[CH3:27][O:28][C:29](Cl)=[O:30].[Cl-].[NH4+]>O1CCCC1>[CH3:19][C:18]([O:7][C:6]([NH:5][C:9]1[C:10]([C:29]([O:28][CH3:27])=[O:30])=[C:11]([F:16])[C:12]([F:15])=[CH:13][CH:14]=1)=[O:8])([CH3:21])[CH3:20]

Participants

7

Reactant 5

HCID 6586Methyl chloroformateHCID 8003PentaneHCID 25517Ammonium ChlorideHCID 73012054HCID 73012054, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 59441840HCID 59441840, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,1-dimethylethyl(3,4-difluorophenyl)carbamate (8.0 g, 35 mmol) in tetrahydrofuran (250 mL) at −78° C. was slowly added tBuLi as a 1.7M solution in pentane (46 mL, 78.60 mmol, 2.25 equiv., Aldrich). The resulting bright yellow solution was maintained at −78° C. for 3 hours, at which time methylchloroformate (3.24 mL, 42 mmol, 1.20 equiv.) was added dropwise. After 45 minutes, aqueous ammonium chloride (100 mL) was added and the reaction was warmed to room temperature. The organic layer was washed with brine, taken to a residue under reduced pressure, and purified by chromatography on SiO2 (10 to 30% ethyl acetate/hexanes) to afford methyl 6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2,3-difluorobenzoate as a pale yellow oil (5.8 g, 20.2 mmol, 58% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (s, 9 H), 3.94 (s, 3 H), 7.21-7.28 (m, 1 H), 8.08 (ddd, J=9.25, 4.12, 2.20 Hz, 1 H), 9.44 (s, 1 H).

Workup

  1. customat −78° C.
  2. additionwas added dropwise
  3. washThe organic layer was washed with brine
  4. custompurified by chromatography on SiO2 (10 to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d7c1ab02b77541e2ae93c800765d13e5
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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