Triethylamine hydrochloride → (S)-tert-Butyl 5-[(3,5-bistrifluoromethylbenzyl)-(2H-tetrazol-5-yl)amino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

HRID 507034Notes

Reaction equation

HRID 507034 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]([C:31]#[N:32])[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:10]2[CH:22]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:24]([CH3:26])=[CH:25][C:9]1=2.Cl.C(N(CC)CC)C.[N-:50]=[N+:51]=[N-:52].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:37][C:36]([F:39])([F:38])[C:34]1[CH:33]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:40])[F:41])[CH:35]=1)[CH2:6][N:7]([C:31]1[N:50]=[N:51][NH:52][N:32]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])[C:10]2[CH:22]=[C:23]([C:27]([F:28])([F:29])[F:30])[C:24]([CH3:26])=[CH:25][C:9]1=2

Participants

6

Reactant 3

HCID 11130Triethylamine hydrochlorideHCID 33557Sodium AzideHCID 59432409(S)-tert-butyl 5-[(3,5-bistrifluoromethylbenzyl)cyanoamino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate

Product 1

HCID 59432487(S)-tert-Butyl 5-[(3,5-bistrifluoromethylbenzyl)-(2H-tetrazol-5-yl)amino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylateYield 99%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Heat a mixture of (S)-tert-butyl 5-[(3,5-bistrifluoromethylbenzyl)cyanoamino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (2.0 g, 3.36 mmol), triethylamine hydrochloride (694 mg, 5.04 mmol) and sodium azide (328 mg, 5.04 mmol) in anhydrous toluene (20 mL) at reflux under nitrogen for 12 h. Dilute the cooled mixture with ethyl acetate (100 mL) and wash with 2 N HCl (2×50 mL), water (50 mL) and brine (50 mL) and dry over anhydrous sodium sulfate. Filter and remove the solvent under reduced pressure to provide the title compound as an off-white foam (2.12 g, >99%), which is used in the next step without purification. ESI MS m/z 637 (M−H)−.

Workup

  1. temperatureHeat
  2. temperatureat reflux under nitrogen for 12 h
  3. washwash with 2 N HCl (2×50 mL), water (50 mL) and brine (50 mL)
  4. dry with materialdry over anhydrous sodium sulfate
  5. filtrationFilter
  6. customremove the solvent under reduced pressure

Sources & evidence

ORD record
ord-60203a9ecb0f4f5fa7f0726c7997aea6
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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