2,4,6-Trifluorobenzoyl chloride → HCID 66939002, compound

HRID 1591888Notes

Reaction equation

HRID 1591888 reaction equation
[ClH:1].Cl.Cl.[CH3:4][N:5]1[CH2:10][CH2:9][CH:8]([N:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([NH2:19])[CH:14]=2)[CH3:12])[CH2:7][CH2:6]1.[F:20][C:21]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[C:22]=1[C:23]([Cl:25])=[O:24]>CO>[ClH:25].[ClH:1].[F:20][C:21]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[C:22]=1[C:23]([NH:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([N:11]([CH3:12])[CH:8]2[CH2:7][CH2:6][N:5]([CH3:4])[CH2:10][CH2:9]2)[CH:14]=1)=[O:24]

Participants

4

Reactant 2

HCID 1448952,4,6-Trifluorobenzoyl chlorideHCID 66938718HCID 66938718, compound

Product 1

HCID 66939002HCID 66939002, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
106.5 °C

Procedure

Load 1-methyl-4-(N-(3-aminophenyl)-N-methylamino)piperidine trihydrochloride (Preparation 11, 240 mg, 1.094 mmol) in methanol (2 ml) onto a SCX column (2 g cartridge, Varian). Elute with ammonia (2.0 M in methanol) to obtain the corresponding free base. Concentrate to dryness. Dissolve the resulting brown oil in dioxane (2 mL) and divide the solution into two aliquots (2×1 mL). Take one of the aliquots and add dioxane (1 mL). Add 2,4,6-trifluoro-benzoyl chloride (0.052 mL, 0.401 mmol) neat. Shake and heat at 106.5° C. for 2 hr. Cool to ambient temperature and load onto a SCX column (1 g cartridge, Varian). Elute with ammonia (2.0 M in methanol). Purify further by flash chromatography using 20/1 mixture of dichloromethane and 2.0 M ammonia in methanolto provide the free base of the title compound (86 mg, 62%). Following a salt formation method similar to Example 1 gives the title compound as a white solid (99 mg): mp 199–200° C.; mass spectrum (free base, ion spray): m/z=378.2 (M+1), 1H NMR (free base, CDCl3): 7.44 (bs, N—H), 7.31 (bs, 1H), 7.19 (t, J=8.3 Hz, 1H), 6.80–6.73 (m, 3H), 6.60 (dd, J=2.2 Hz, 8.3 Hz, 1H), 3.64 (tt, J=4.0 Hz, 11.9 Hz, 1H), 3.05 (bd, J=10.8 Hz, 2H), 2.81 (s, 3H), 2.38 (s, 3H), 2.28–2.17 (bm, 2H), 2.06–1.92 (bm, 2H), 1.76 (bd, J=12.2 Hz, 2H).

Workup

  1. washElute with ammonia (2.0 M in methanol)
  2. customto obtain the corresponding free base
  3. concentrationConcentrate to dryness
  4. dissolutionDissolve the resulting brown oil in dioxane (2 mL)
  5. additionadd dioxane (1 mL)
  6. temperatureCool to ambient temperature
  7. washElute with ammonia (2.0 M in methanol)
  8. customPurify further by flash chromatography
  9. addition20/1 mixture of dichloromethane and 2.0 M ammonia in methanolto

Sources & evidence

ORD record
ord-1683d163ed26410688c1544c217e8469
Source dataset
uspto-grants-2007_11
Patent number
US07291632B2

Reaction notes

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