p-Aminoacetophenone → tert-Butyl N-{2-{(4-acetylphenyl)amino}-2-oxoethyl}-N-(phenylmethyl)carbamate

HRID 1595268Notes

Reaction equation

HRID 1595268 reaction equation
ClC(OCC(C)C)=O.O[C:10](=[O:27])[CH2:11][N:12]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16].CCN(CC)CC.[NH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42](=[O:44])[CH3:43])=[CH:38][CH:37]=1>C(Cl)Cl.O>[C:42]([C:39]1[CH:40]=[CH:41][C:36]([NH:35][C:10](=[O:27])[CH2:11][N:12]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[CH:37][CH:38]=1)(=[O:44])[CH3:43]

Participants

7

Reactant 4

HCID 7468p-AminoacetophenoneHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 105158162-(Benzyl(tert-butoxycarbonyl)amino)acetic acid

Product 1

HCID 18369528tert-Butyl N-{2-{(4-acetylphenyl)amino}-2-oxoethyl}-N-(phenylmethyl)carbamateYield 61.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Isobutyl chloroformate (35.1 g, 0.26 mol) was added (15 min) to an ice-cold solution of tert-butyl N-(2-hydroxy-2-oxoethyl)-N-(phenylmethyl)carbamate (65.0 g, 0.24 mol), described in preceding section a), and Et3N (31.0 g, 0.31 mol) in CH2Cl2 (610 mL). The mixture was stirred at 0° for 45 min. Solid 4′-aminoacetophenone (34.8 g, 0.26 mol) was added portion wise to the reaction mixture. The reaction mixture was stirred at 0° for 1.5 h and then at room temperature for 16 h. H2O (10 mL) was added. The resulting solution was concentrated under reduced pressure. The residue was dissolved in EtOAc (1 L). The solution was washed successively with 1 N aqueous HCl (2×300 mL), a saturated aqueous solution of NaHCO3 (2×300 mL) and brine (200 mL), dried (MgSO4) and concentrated under reduced pressure. The resulting brownish solid was crystallized (EtOAc: Hex) to give the title compound (56.8 g, 61% yield) as a white solid: 1H NMR (400 MHz, CDCl3) δ9.72 (broad s, 1H), 7.90 (d, J=8.6 Hz, 2H), 7.40-7.54 (m, 2H), 7.26-7.39 (m, 5H), 4.55 (s, 2H), 3.96 (s, 2H), 2.56 (s, 3H), 1.51 (s, 9H); MS (FAB) m/z383 (MH)+.

Workup

  1. stirringThe reaction mixture was stirred at 0° for 1.5 h
  2. waitat room temperature for 16 h
  3. concentrationThe resulting solution was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in EtOAc (1 L)
  5. washThe solution was washed successively with 1 N aqueous HCl (2×300 mL)
  6. dry with materiala saturated aqueous solution of NaHCO3 (2×300 mL) and brine (200 mL), dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting brownish solid was crystallized (EtOAc: Hex)

Sources & evidence

ORD record
ord-4ee295a93d084ae385562a077a0a299d
Source dataset
uspto-grants-2001_09
Patent number
US06288091B1

Reaction notes

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