Methyl chloroformate → HCID 59441788, compound

HRID 1014169Notes

Reaction equation

HRID 1014169 reaction equation
[CH3:1][C:2]([N:5]([C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([Cl:16])[CH:10]=1)[C:6](=[O:8])[O-:7])([CH3:4])[CH3:3].[Li][C:18]([CH3:21])([CH3:20])[CH3:19].CCCCC.[CH3:27][O:28][C:29](Cl)=[O:30].[Cl-].[NH4+]>O1CCCC1>[Cl:16][C:11]1[CH:12]=[C:13]([F:15])[C:14]([C:29]([O:28][CH3:27])=[O:30])=[C:9]([NH:5][C:6]([O:7][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:8])[CH:10]=1.[CH3:4][C:2]([N:5]([C:9]1[CH:10]=[C:11]([Cl:16])[CH:12]=[C:13]([F:15])[C:14]=1[C:29](=[O:30])[C:18]([CH3:21])([CH3:20])[CH3:19])[C:6](=[O:7])[O-:8])([CH3:1])[CH3:3]

Participants

8

Reactant 5

HCID 6586Methyl chloroformateHCID 8003PentaneHCID 25517Ammonium ChlorideHCID 86644178HCID 86644178, compoundHCID 178418306HCID 178418306, compound

Product 2

HCID 59441788HCID 59441788, compoundHCID 86644177HCID 86644177, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,1-dimethylethyl(3-chloro-5-fluorophenyl)carbamate (7.34 g, 30 mmol) in tetrahydrofuran (200 mL, Aldrich) at −78° C. was slowly added tBuLi as a 1.7M solution in pentane (46 mL, 78 mmol, 2.6 equiv.). The resulting bright yellow solution was maintained at −78° C. for 3 hours, at which time methylchloroformate (3.02 mL, 39 mmol, Fluka) 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 4-chloro-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-fluorobenzoate as a pale yellow oil (6.4, 70% yield) as a roughly 5:1 mixture with 1,1-dimethylethyl[5-chloro-2-(2,2-dimethylpropanoyl)-3-fluorophenyl]carbamate which was removed in the subsequent step. 1H NMR (400 MHz, CDCl3) δ ppm 1.52 (s, 9 H), 3.95 (s, 3 H), 6.76 (d, J=2.20 Hz, 1 H), 6.78 (d, J=4 Hz, 1H) 8.31-8.34 (m, 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-46e0121a60a74531999bf98e4a927520
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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