Water → Ethyl 3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]-4-nitrobutanoate

HRID 1499953Notes

Reaction equation

HRID 1499953 reaction equation
[Cl:1][C:2]1[C:3]([F:24])=[C:4](/[CH:17]=[CH:18]/[C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:5]([O:14][CH2:15][CH3:16])=[C:6]([C:8]2([CH3:13])[O:12][CH2:11][CH2:10][O:9]2)[CH:7]=1.N12CCCN=C1CCCCC2.O.[N+:37]([CH3:40])([O-:39])=[O:38]>>[Cl:1][C:2]1[C:3]([F:24])=[C:4]([CH:17]([CH2:40][N+:37]([O-:39])=[O:38])[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:5]([O:14][CH2:15][CH3:16])=[C:6]([C:8]2([CH3:13])[O:9][CH2:10][CH2:11][O:12]2)[CH:7]=1

Participants

5

Reactant 4

HCID 962WaterHCID 6375NitromethaneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86677867Ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]acrylate

Product 1

HCID 86677869Ethyl 3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]-4-nitrobutanoate

Conditions

Temperature
60 °C

Procedure

A solution ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl\) phenyl]acrylate (10 g, 28 mmol) (from Step 2) in nitromethane (100 mL) was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (4.6 mL, 31 mmol) and stirred at 60° C. for 15 h. The reaction mixture was poured into water (400 mL) and extracted with ethyl acetate (2×300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude orange oil. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-30%) to give the desired product as a mixture of enantiomers (10.4 g, 89%). 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J=9.1 Hz, 1H), 4.82 (ddd, J=12.5, 7.6, 1.4 Hz, 1H), 4.68 (dd, J=12.5, 7.2 Hz, 1H), 4.54-4.40 (m, 1H), 4.15-3.90 (m, 6H), 3.89-3.75 (m, 2H), 2.85 (ddd, J=16.0, 8.6, 1.4 Hz, 1H), 2.73 (dd, J=16.1, 6.2 Hz, 1H), 1.70 (s, 3H), 1.47 (t, J=7.0 Hz, 3H), 1.21 (t, J=7.1 Hz, 3H). LCMS for C18H24ClFNO7 (M+H)+: m/z=420.1; Found: 420.1.

Workup

  1. extractionextracted with ethyl acetate (2×300 mL)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a crude orange oil
  6. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-21c4c94921484da0abc8941855b405df
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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