Acetic Acid → (S)-5-(3-fluoro-5-trifluoromethyl-benzylamino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester

HRID 507176Notes

Reaction equation

HRID 507176 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH:19]=O.C(O)(=O)C.[NH2:32][C@H:33]1[CH2:39][CH2:38][CH2:37][N:36]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:35]2[CH:47]=[C:48]([C:52]([F:55])([F:54])[F:53])[C:49]([CH3:51])=[CH:50][C:34]1=2.C(=O)(O)[O-].[Na+]>ClC(Cl)C>[C:43]([O:42][C:40]([N:36]1[CH2:37][CH2:38][CH2:39][C@H:33]([NH:32][CH2:19][C:18]2[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=[C:16]([F:15])[CH:17]=2)[C:34]2[CH:50]=[C:49]([CH3:51])[C:48]([C:52]([F:55])([F:53])[F:54])=[CH:47][C:35]1=2)=[O:41])([CH3:46])([CH3:45])[CH3:44]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 6056863-Fluoro-5-(trifluoromethyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59432516(S)-tert-Butyl 5-amino-7-methyl-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate

Product 1

HCID 59432467(S)-5-(3-fluoro-5-trifluoromethyl-benzylamino)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Add sodium triacetoxyborohydride (0.40 g, 1.89 mmol) to a mixture of 3-fluoro-5-trifluoromethyl benzaldehyde (0.096 mL, 0.69 mmol), acetic acid (0.030 mL, 0.625 mmol)) and (S)-tert-Butyl 5-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (Example 3, Step 13) (0.215 g, 0.63 mmol) in dichloroethane (3.0 mL). Stir the mixture at room temperature under an atmosphere of nitrogen for 20 h. Add a saturated solution of sodium bicarbonate, separate the layers and extract the aqueous layer with dichloromethane. Dry the combined organic layers over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate (gradient eluent, 0-30% ethyl acetate in hexane), to afford the title compound (0.32 g, 98%). MS (ES+): 521 (M+H).

Workup

  1. customseparate the layers
  2. extractionextract the aqueous layer with dichloromethane
  3. dry with materialDry the combined organic layers over anhydrous sodium sulfate
  4. filtrationfilter
  5. customremove the solvent under reduced pressure
  6. customPurify the residue by flash chromatography
  7. washeluting with hexanes/ethyl acetate (gradient eluent, 0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-b079fc63019947bcb4c3b95125aca588
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

Loading…