Chloroacetone → Benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamate

HRID 2068540Notes

Reaction equation

HRID 2068540 reaction equation
[OH-].[K+].[O:3]=[C:4]1[C@H:10]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9][CH2:8][C:7]2[CH:22]=[CH:23][CH:24]=[CH:25][C:6]=2[NH:5]1.Cl[CH2:27][C:28](=[O:30])[CH3:29].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH2:27]([N:5]1[C:6]2[CH:25]=[CH:24][CH:23]=[CH:22][C:7]=2[CH2:8][CH2:9][C@@H:10]([NH:11][C:12](=[O:21])[O:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:4]1=[O:3])[C:28]([CH3:29])=[O:30]

Participants

6

Reactant 4

HCID 6571Chloroacetone2×HCID 14797Potassium Hydroxide2×HCID 2724141Tetrabutylammonium Fluoride2×HCID 58304068Benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate

Product 1

HCID 58304091Benzyl N-[(3R)-1-acetonyl-2-oxo-4,5-dihydro-3H-1-benzazepin-3-yl]carbamateYield 69.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add powdered potassium hydroxide (KOH) (0.72 g, 12.89 mmol) to a solution of benzyl N-[(3R)-2-oxo-1,3,4,5-tetrahydro-1-benzazepin-3-yl]carbamate (2.0 g, 6.44 mmol), chloroacetone (1.19 g, 12.89 mmol), and tetrabutylammonium fluoride (1.29 mL, 1.29 mmol, 1M solution in THF) in tetrahydrofuran (65 mL). Stir the mixture for approximately 16 hours at ambient temperature. Add additional potassium hydroxide (0.361 g, 6.44 mmol), chloroacetone (0.59 g, 6.44 mmol), tetrabutylammonium fluoride (0.65 mL, 0.65 mmol, 1M solution in THF) and THF (20 mL) to the reaction and stir for approximately 48 hours at ambient temperature. Filter the reaction mixture through diatomaceous earth and concentrate the filtrate under reduced pressure. Purify the residue by flash chromatography (10% ethyl acetate/hexane to 100% ethyl acetate) to give the title compound (1.64 g, 65%): MS (m/z): 389 (M+23).

Workup

  1. customto the reaction
  2. stirringstir for approximately 48 hours at ambient temperature
  3. filtrationFilter the reaction mixture through diatomaceous earth
  4. concentrationconcentrate the filtrate under reduced pressure
  5. customPurify the residue by flash chromatography (10% ethyl acetate/hexane to 100% ethyl acetate)

Sources & evidence

ORD record
ord-2b6dccf1474a43aeb4047504dd16a12d
Source dataset
uspto-grants-2012_10
Patent number
US08299061B2

Reaction notes

Loading…