Benzaldehyde → 3(R)-(benzylamino)-2,3,4,5-tetrahydro-1H-benzazepin-2-one

HRID 1033405Notes

Reaction equation

HRID 1033405 reaction equation
[NH2:1][C@@H:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:13].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.FC(F)(F)C(O)=O.[Na]>CO.C1COCC1>[CH2:14]([NH:1][C@@H:2]1[CH2:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[NH:4][C:3]1=[O:13])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 6422Trifluoroacetic acidHCID 5360545SodiumHCID 10103689(R)-3-amino-4,5-dihydro-1H-benzo[b]azepin-2(3H)-one

Product 1

HCID 544972723(R)-(benzylamino)-2,3,4,5-tetrahydro-1H-benzazepin-2-oneYield 51.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 528 mg (3.0 mmol) of 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Example 1, Step B) in 45 mL of absolute methanol at room temperature was treated with 4.5 g of powdered 3A molecular sieves followed by dropwise addition of a solution of 954 mg (9.0 mmol, 3 eq.) of benzaldehyde in 15 mL of methanol. The pH of the mixture was adjusted to 7 by addition of trifluoroacetic acid then stirred at room temperature for 2 hours. Sodium cynaoborohydride (18 mL of 1.0M THF solution: 18 mmol, 6 eq.) was added and the mixture stirred at room temperature for 18 hours. The mixture was filtered and the filtrate treated with 3 mL of trifluoroacetic acid with stirring for 3 hours, then all volatiles removed under vacuum and the residue dissolved in 50 mL of ethyl acetate. The ethyl acetate solution was washed with water (3×15 mL), saturated aqueous sodium bicarbonate (2×15 mL) and 15 mL of brine then dried over magnesium sulfate, filtered and solvents removed under vacuum. The residue was purified by chromatography on silica, eluting with ethyl acetate/hexane (70:30), to afford 410 mg (1.54 mmol, 51%) of the product. 1H NMR (200MHz,CDCl3): 2.05 (m,1H), 2.5-3.0 (m,3H), 3.37 (dd;7.11Hz;1H), 3.57 (d,12Hz,1H), 3.90 (d,12Hz,1H), 7.05 (d,8Hz,1H), 7.1-7.4 (m,8H), 7.75 (br s,1H). FAB-MS: calculated for C17H18N2O 266; found 267 (M+H,75%).

Workup

  1. stirringthe mixture stirred at room temperature for 18 hours
  2. filtrationThe mixture was filtered
  3. additionthe filtrate treated with 3 mL of trifluoroacetic acid
  4. stirringwith stirring for 3 hours
  5. customall volatiles removed under vacuum
  6. dissolutionthe residue dissolved in 50 mL of ethyl acetate
  7. washThe ethyl acetate solution was washed with water (3×15 mL), saturated aqueous sodium bicarbonate (2×15 mL) and 15 mL of brine
  8. dry with materialthen dried over magnesium sulfate
  9. filtrationfiltered
  10. customsolvents removed under vacuum
  11. customThe residue was purified by chromatography on silica
  12. washeluting with ethyl acetate/hexane (70:30)

Sources & evidence

ORD record
ord-fa2455ee68c04a22b72aa5f7c05ef801
Source dataset
uspto-grants-1994_05
Patent number
US05310737

Reaction notes

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