Methyl chloroformate → HCID 4928092, compound

HRID 889432Notes

Reaction equation

HRID 889432 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH2:4].CCN(C(C)C)C(C)C.Cl[C:22]([O:24][CH3:25])=[O:23]>C1COCC1>[F:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH:4][C:22](=[O:23])[O:24][CH3:25]

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 677852-Fluoro-5-nitroanilineHCID 81531Diisopropylethylamine

Product 1

HCID 4928092HCID 4928092, compoundYield 65.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-fluoro-5-nitroaniline (500 mg, 3.20 mmol) in THF (20 mL) was treated with DIEA (0.84 mL, 4.8 mmol) followed by methyl chloroformate (0.25 mL, 3.20 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The crude product was dissolved in a small amount of DCM and purified by flash chromatography (SiO2, 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes, 40 g column, 30 min. gradient) to afford Intermediate 59A (450 mg, 65.6%). HPLC: Rt=2.868 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.94 (1H, s), 8.72 (1H, dd, J=6.80, 2.77 Hz), 7.87-8.09 (1H, m), 7.52 (1H, t), 3.72 (3H, s).

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe crude product was dissolved in a small amount of DCM
  3. custompurified by flash chromatography (SiO2, 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes, 40 g column, 30 min. gradient)

Sources & evidence

ORD record
ord-7c8f0079f96b4658bc0ecb4da8f3315b
Source dataset
uspto-grants-2012_08
Patent number
US08252795B2

Reaction notes

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