Water → HCID 57995558, compound

HRID 1183634Notes

Reaction equation

HRID 1183634 reaction equation
[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[C:7]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[CH:6]=1.Br[CH2:22][CH:23]1[CH2:26][CH2:25][CH2:24]1.[OH-].[K+].O>CS(C)=O>[CH3:1][O:2][C:3](=[O:20])[CH:4]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[C:7]([O:14][CH2:15][C:16]([F:17])([F:19])[F:18])[CH:6]=1)[CH2:22][CH:23]1[CH2:26][CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 2734658(Bromomethyl)cyclobutaneHCID 57995515HCID 57995515, compound

Product 1

HCID 57995558HCID 57995558, compoundYield 43.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

[4-Nitro-3-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid methyl ester (33 g, 94.5 mmol) and (bromomethyl)cyclobutane (17 g, 114.1 mmol) were mixed in DMSO (50 mL) and KOH (6.4 g, 114.1 mmol) was added in portions over 15 min. The reaction mixture was stirred for 16 h and water (100 mL) was added. The reaction mixture was extracted with EtOAc (3×50 mL). The combined organic phases were dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography using Heptane-EtOAc (9:1-4:1) to give 15 g (40%) of the product as a yellow oil. (The synthesis was repeated with temperature kept at 40° C. over 16 h to give the product in quantitative yield). 1H NMR (300 MHz, CDCl3/TMS): δ 7.86 (d, J=8.0 Hz, 1H), 7.12-7.09 (m, 2H), 4.50 (q, J=7.7 Hz, 2H), 3.68 (s, 3H), 3.55 (t, J=7.3 Hz, 1H), 2.22-2.10 (m, 2H), 2.03-1.75 (m, 5H), 1.70-1.55 (m, 2H). 13C NMR (75 MHz, CDCl3/TMS): δ 172.9, 150.5, 146.4, 139.4, 126.0, 122.7, 122.6 (d, 1JCF=277.6 Hz), 116.0, 67.5 (q, 1JCF=36.7 Hz), 52.3, 49.6, 40.7, 33.9, 28.2, 27.9, 18.4.

Workup

  1. extractionThe reaction mixture was extracted with EtOAc (3×50 mL)
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. customevaporated
  4. customto give a crude yellow oil, which
  5. customwas purified by silica gel gradient column chromatography

Sources & evidence

ORD record
ord-199f341d1dde46dba3f15a459025dfce
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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