Diisopropylethylamine → 2-Methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-carboxaldehyde

HRID 2215112Notes

Reaction equation

HRID 2215112 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8](O)=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([F:20])([F:19])[F:18].C1C=CN2CC3C=CC=CC=3NCC=12.C(N(CC)C(C)C)(C)C>S(Cl)(Cl)=O.ClCCl>[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([F:18])([F:19])[F:20]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepineHCID 219478123-Methyl-4-[2-(trifluoromethyl)phenyl]benzoic acid

Product 1

HCID 586096482-Methyl-2′-(trifluoromethyl)[1,1′-biphenyl]-4-carboxaldehydeYield 116.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A suspension of (2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carboxylic acid of Step C (0.50 g, 1.78 mmol) in thionyl chloride (3 mL) was heated at reflux for 90 minutes. After cooling, the thionyl chloride was removed in vacuo and the residue dissolved in toluene. The solution was concentrated in vacuo to yield the crude acid chloride as a brown oil. The acid chloride was dissolved in dichloromethane (5 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.49 g, 2.66 mmol) and N,N-diisopropylethyl amine (0.68 mL, 3.90 mmol) in dichloromethane (15 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was sequentially washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane gave a white foam which was crystallized upon sonication in ethanol/hexane to provide the title compound (0.55 g) as a white solid, m.p. 127–130° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 90 minutes
  3. temperatureAfter cooling
  4. customthe thionyl chloride was removed in vacuo
  5. dissolutionthe residue dissolved in toluene
  6. concentrationThe solution was concentrated in vacuo
  7. customto yield the crude acid chloride as a brown oil
  8. customthe reaction was quenched with water
  9. washThe organic layer was sequentially washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give a yellow foam
  14. customPurification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane
  15. customgave a white foam which
  16. customwas crystallized upon sonication in ethanol/hexane

Sources & evidence

ORD record
ord-fbffcaa7cf9340b2b53ae6488a31e6b0
Source dataset
uspto-grants-2006_09
Patent number
US07109193B2

Reaction notes

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