p-Toluenesulfonic acid → HCID 59432423, compound

HRID 507141Notes

Reaction equation

HRID 507141 reaction equation
[CH3:1][C:2]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][C:5]2[N:6]([C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])[CH2:7][CH2:8][CH2:9][C:10](=O)[C:4]=2[CH:3]=1.[NH2:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1>[CH:15]([O:14][C:12]([N:6]1[CH2:7][CH2:8][CH2:9][CH:10]([NH:24][C:25]2[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=2)[C:4]2[CH:3]=[C:2]([CH3:1])[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][C:5]1=2)=[O:13])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 100093-AminopyridineHCID 4311764Sodium borohydrideHCID 59432498Propan-2-yl 7-methyl-5-oxo-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-1-benzazepine-1-carboxylate

Product 1

HCID 59432423HCID 59432423, compoundYield 13.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

Add isopropyl 7-methyl-5-oxo-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (Example 3, Step 8) (1.16 g, 3.52 mmol), 3-aminopyridine (465 mg, 5.10 mmol), p-toluenesulfonic acid (210 mg, 1.10 mmol) and toluene (8.0 mL) to a sealed tube and stir vigorously for 4 days at 130° C. Evaporate the toluene, dissolve the residue with MeOH (10.0 mL), and add sodium borohydride (146 mg, 3.86 mmol) portionwise. Reflux overnight and evaporate the MeOH. Partition the resulting residue between water (10 mL) and EtOAc (10 mL). Wash the organic layer with 2-mL portions of water and brine, dry (MgSO4), and concentrate. Purify via column chromatography (silica gel; 30% to 70% EtOAc:hexanes to 100% EtOAc gradient) to give 189 mg (13%) of the title compound as a white solid. APCI MS m/z 408 [M+H]+.

Workup

  1. customEvaporate the toluene
  2. dissolutiondissolve the residue with MeOH (10.0 mL)
  3. temperatureReflux overnight
  4. customevaporate the MeOH
  5. customPartition the resulting residue between water (10 mL) and EtOAc (10 mL)
  6. washWash the organic layer with 2-mL portions of water and brine
  7. dry with materialdry (MgSO4)
  8. concentrationconcentrate
  9. customPurify via column chromatography (silica gel; 30% to 70% EtOAc:hexanes to 100% EtOAc gradient)

Sources & evidence

ORD record
ord-69f151742ab54c6d838f6539154594d6
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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