Water → 7-[4-(4-Butyl-phenylethynyl)-benzylamino]-2,2-dimethyl-benzo[1,3]dioxin-4-one

HRID 551928Notes

Reaction equation

HRID 551928 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[NH2:21][C:22]1[CH:23]=[CH:24][C:25]2[C:30](=[O:31])[O:29][C:28]([CH3:33])([CH3:32])[O:27][C:26]=2[CH:34]=1.O.[BH4-].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:20]=[CH:19][C:16]([CH2:17][NH:21][C:22]3[CH:23]=[CH:24][C:25]4[C:30](=[O:31])[O:29][C:28]([CH3:32])([CH3:33])[O:27][C:26]=4[CH:34]=3)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 4311764Sodium borohydrideHCID 113345124-[2-(4-Butylphenyl)ethynyl]benzaldehydeHCID 231100727-Amino-2,2-dimethyl-4H-1,3-benzodioxine-4-one

Product 1

HCID 114192887-[4-(4-Butyl-phenylethynyl)-benzylamino]-2,2-dimethyl-benzo[1,3]dioxin-4-oneYield 66%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-[(4-butylphenyl)ethynyl]benzaldehyde (2.0 g, 7.63 mmol, intermediate which may be obtained according to methods disclosed in EP03103780.7) and 7-amino-2,2-dimethyl-4H-1,3-benzodioxine-4-one (1.47 g, 7.63 mmol) in toluene (30 mL) was heated at reflux for 96 hrs with azeotropic removal of water. The reaction mixture was concentrated off under reduced pressure. MeOH (15 mL) and THF (15 mL) were then added, and the resulting mixture chilled at 0° C. Sodium borohydride (375 mg, 9.9 mmol) was added portionwise and the mixture was stirred for 1 hr at 0° C., then 3 hrs at room temperature. The reaction mixture was diluted with EtOAc (60 mL) and washed with an aqueous solution of NaOH (3×15 mL, 1N). The organic layer was dried over MgSO4 and the solvents were removed under reduced pressure. Et2O (100 mL) was added and the resulting white precipitate was filtered off to give 2.2 g (66%) of the title compound as a white solid. HPLC, Rt: 5.62 min (purity: 93.6%). LC/MS, M−(ESI): 438.3, M+(ESI): 440.2. 1H NMR (CDCl3) δ: 7.71 (d, J=8.6 Hz, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.42 (d, J=8.3 Hz, 2H), 7.29 (d, J=7.9 Hz, 2H), 7.14 (d, J=7.9 Hz, 2H), 6.32 (m, 1H), 6.01 (m, 1H), 4.38 (s, 2H), 2.61 (t, J=7.5 Hz, 2H), 1.60 (s, 6H), 1.65-1.50 (m, 2H), 1.42-1.28 (m, 2H), 0.91 (t, J=7.5 Hz, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated off under reduced pressure
  2. additionMeOH (15 mL) and THF (15 mL) were then added
  3. custom3 hrs
  4. customat room temperature
  5. washwashed with an aqueous solution of NaOH (3×15 mL, 1N)
  6. dry with materialThe organic layer was dried over MgSO4
  7. customthe solvents were removed under reduced pressure
  8. additionEt2O (100 mL) was added
  9. filtrationthe resulting white precipitate was filtered off

Sources & evidence

ORD record
ord-e55277c7d7d34a359e77530798631efd
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

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