Trifluoroacetic acid → 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride

HRID 1514262Notes

Reaction equation

HRID 1514262 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:27]4[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22][C:21]=4[CH:20]=[CH:19][CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].FC(F)(F)C(O)=O>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[C:27]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22][C:21]=4[CH:20]=[CH:19][CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 594034711,1-Dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

Product 1

HCID 684679086-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochlorideYield 199.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,1-Dimethylethyl 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (Preparation 17) (260 mg, 0.537 mmol) was dissolved in DCM (20 ml) and treated with trifluoroacetic acid (2 ml, 26.0 mmol). The resulting mixture was heated at reflux for 1 hour then evaporated. The resulting residue was partitioned between DCM (10 ml) and 2N NaOH (10 ml). The DCM layer was collected, dried (hydrophobic frit) and evaporated. The free-base was dissolved in 4M HCl in dioxane and evaporated to give the HCl salt, 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (225 mg, 0.535 mmol, 100% yield) as an off-white powder. δH (400 MHz, CDCl3) 10.10 (2H, br.s), 8.18 (1H, s), 8.02 (1H, d), 7.82-7.80 (1H, m), 7.33-7.22 (2H, m), 7.05 (1H, d), 5.30 (2H, s), 4.76-4.64 (1H, m), 3.8-3.65 (2H, m), 3.48-3.3 (4H, m), 1.45 (6H, d); MS (ES) C21H2235ClN3O2 requires 383; found 384 [M+H]+.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 1 hour
  3. customthen evaporated
  4. customThe resulting residue was partitioned between DCM (10 ml) and 2N NaOH (10 ml)
  5. customThe DCM layer was collected
  6. customdried (hydrophobic frit)
  7. customevaporated
  8. dissolutionThe free-base was dissolved in 4M HCl in dioxane
  9. customevaporated

Sources & evidence

ORD record
ord-46e32b24074a46ba9885043cab92f365
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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