3,5-Bis(trifluoromethyl)benzaldehyde → HCID 59432389, compound

HRID 507056Notes

Reaction equation

HRID 507056 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[CH:6]=O.[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][CH2:28][C@H:27]([NH2:31])[C:26]2[CH:32]=[C:33]([CH2:40][CH3:41])[C:34]([C:36]([F:39])([F:38])[F:37])=[CH:35][C:25]1=2)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[C:17]([O:21][C:22]([N:24]1[CH2:30][CH2:29][CH2:28][C@H:27]([NH:31][CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:16])([F:15])[F:1])[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=2)[C:26]2[CH:32]=[C:33]([CH2:40][CH3:41])[C:34]([C:36]([F:39])([F:37])[F:38])=[CH:35][C:25]1=2)=[O:23])([CH3:20])([CH3:19])[CH3:18]

Participants

6

Reactant 3

HCID 1362473,5-Bis(trifluoromethyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59432521HCID 59432521, compound

Product 1

HCID 59432389HCID 59432389, compoundYield 82.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

Add 3,5-bistrifluoromethylbenzaldehyde (4.30 g, 24.22 mmol) to a solution of (S)-5-amino-7-ethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tert-butyl ester (4.91 g, 13.70 mmol) in dichloromethane (100 mL) and glacial acetic acid (6 mL) at room temperature under nitrogen and stir for 2 h. Add sodium triacetoxyborohydride (6.01 g, 28.35 mmol) and stir the mixture for 2 h. Remove the solvents under reduced pressure and dilute the residue with dichloromethane (50 mL) and water (50 mL). Collect the organic layer and extract the aqueous layer with dichloromethane (3×30 mL). Wash the combined organic extracts with water (20 mL) and brine (20 mL) and dry over anhydrous sodium sulfate. Filter and remove the solvents under reduced pressure to provide the title compound as an amber oil (6.58 g, 75%), which is used in the next step without purification. 1H NMR (CDCl3, 300 MHz) δ 1.21-2.30 (m, 19H), 2.83-2.89 (m, 2H), 4.78-4.80 (m, 3H), 6.89-7.60 (m, 3H), 7.70-7.91 (m, 2H); APCI MS m/z 585 (M+H)+.

Workup

  1. customRemove the solvents under reduced pressure
  2. additiondilute the residue with dichloromethane (50 mL) and water (50 mL)
  3. customCollect the organic layer
  4. extractionextract the aqueous layer with dichloromethane (3×30 mL)
  5. washWash the combined organic extracts with water (20 mL) and brine (20 mL)
  6. dry with materialdry over anhydrous sodium sulfate
  7. filtrationFilter
  8. customremove the solvents under reduced pressure

Sources & evidence

ORD record
ord-414a592dec874709aa529a47ae743b60
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

Loading…