Toluene → HCID 73445650, compound

HRID 460278Notes

Reaction equation

HRID 460278 reaction equation
C1(C)C=CC=CC=1.N1CCCCC1.[CH2:14]([C:18]1[CH:19]=[C:20]([C:29]2[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=2[O:37][C:38]([F:41])([F:40])[F:39])[CH:32]=O)[C:21]2[O:25][CH2:24][C:23]([CH3:27])([CH3:26])[C:22]=2[CH:28]=1)[CH:15]([CH3:17])[CH3:16].[S:42]1[CH2:46][C:45](=[O:47])[NH:44][C:43]1=[O:48]>C(OCC)(=O)C.C(O)(=O)C>[CH2:14]([C:18]1[CH:19]=[C:20]([C:29]2[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=2[O:37][C:38]([F:41])([F:39])[F:40])[CH:32]=[C:46]2[S:42][C:43](=[O:48])[NH:44][C:45]2=[O:47])[C:21]2[O:25][CH2:24][C:23]([CH3:26])([CH3:27])[C:22]=2[CH:28]=1)[CH:15]([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 1140TolueneHCID 5437ThiazolidinedioneHCID 8082PiperidineHCID 22041381HCID 22041381, compound

Product 1

HCID 73445650HCID 73445650, compoundYield 72.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of toluene (35 mL), piperidine (145 μL), acetic acid (145 μL), 3-(5-isobutyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde (5.7 g, 14.53 mmol) and 2,4-thiazolidinedione (1.7 g, 14.53 mmol) was heated at reflux for 20 hrs. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel (0 to 20% ethylacetate in hexane) and further recrystallised from ethanol/water to afford 5.15 g (72%) of 5-[3-(5-Isobutyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzylidene]-thiazolidine-2,4-dione. mp 142–146° C. 1H-NMR (300 MHz, DMSO-d-6): 0.87 (d, J=6.9 Hz, 6H), 1.31 (s, 6H), 1.81 (m, 1H), 2.44 (d, J=6.9 Hz, 2H), 4.19 (s, 2H), 6.91 (d, J=1.5 Hz, 1H), 7.07 (d, J=1.5 Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.70 (dd, J1=8.4 Hz, J2=2.4 Hz, 1H), 7.75 (d, J=2.1 Hz, 1H), 7.86 (s, 1H), 12.70 (br s, 1. The intermediate 3-(5-isobutyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde was prepared as follows:

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 20 hrs
  3. washwashed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was chromatographed on silica gel (0 to 20% ethylacetate in hexane)
  8. customfurther recrystallised from ethanol/water

Sources & evidence

ORD record
ord-0b53b386b4304b32b18a200cc710c7dd
Source dataset
uspto-grants-2007_03
Patent number
US07196108B2

Reaction notes

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