Diiodomethane → Methyl 3-cyclopropoxy-2-nitrobenzoate

HRID 2276865Notes

Reaction equation

HRID 2276865 reaction equation
Cl[C:2](Cl)(Cl)C(O)=O.C([Zn]CC)C.ICI.[N+:16]([C:19]1[C:28]([O:29][CH:30]=[CH2:31])=[CH:27][CH:26]=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22])([O-:18])=[O:17]>ClCCl>[CH:30]1([O:29][C:28]2[C:19]([N+:16]([O-:18])=[O:17])=[C:20]([CH:25]=[CH:26][CH:27]=2)[C:21]([O:23][CH3:24])=[O:22])[CH2:2][CH2:31]1

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 6421Trichloroacetic AcidHCID 90072113Methyl 2-nitro-3-(vinyloxy)benzoateHCID 178418750HCID 178418750, compound

Product 1

HCID 90072167Methyl 3-cyclopropoxy-2-nitrobenzoateYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In a 3 necked, 500 mL flask, a solution of 2,2,2-trichloroacetic acid (16.30 g, 100 mmol) in dichloromethane (100 mL) was slowly added via an addition funnel to a −10° C. solution of diethylzinc (1M hexanes, 100 mL, 100 mmol) under a nitrogen atmosphere. The reaction mixture was stirred for 10 min. Next, diiodomethane (8 mL, 100 mmol) was dropwise added by syringe, and the reaction solution was stirred for 10 min. A solution of methyl 2-nitro-3-(vinyloxy)benzoate (7.42 g, 33.2 mmol) in dichloromethane (20 mL) was added slowly via an addition funnel. The solution was allowed to warm to room temperature overnight. The reaction mixture was cooled to 0° C. and quenched with 1M HCl. The reaction solution was transferred to a separatory funnel, and the aqueous layer extracted with dichloromethane (3×). The combined extracts were washed with saturated sodium bicarbonate, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product mixture was purified by ISCO (0% of EtOAc/heptane in 15 minutes, 220 g column) to provide methyl 3-cyclopropoxy-2-nitrobenzoate (4.7 g, 19.81 mmol, 60.0% yield). HPLC: RT=2.66 min (H2O/MeOH with TFA, SunFire C18 3.5 μm, 2.1×30 mm, gradient=4 min, wavelength=220 nm); MS(ES):m/z=260 [M+Na]+; 1H NMR (400 MHz, chloroform-d) δ 7.68-7.57 (m, 2H), 7.57-7.41 (m, 1H), 4.03-3.82 (m, 4H), 0.94-0.78 (m, 4H).

Workup

  1. stirringthe reaction solution was stirred for 10 min
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customquenched with 1M HCl
  4. customThe reaction solution was transferred to a separatory funnel
  5. extractionthe aqueous layer extracted with dichloromethane (3×)
  6. washThe combined extracts were washed with saturated sodium bicarbonate, water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product mixture was purified by ISCO (0% of EtOAc/heptane in 15 minutes, 220 g column)

Sources & evidence

ORD record
ord-0b1a141f4cb64180b3a54485b05d2f24
Source dataset
uspto-grants-2015_09
Patent number
US09133139B2

Reaction notes

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