Sodium Chloride → 6-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one

HRID 551888

Reaction equation

HRID 551888 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:34]=[CH:33][C:25]2[O:26][C:27]([CH3:32])([CH3:31])[O:28][C:29](=[O:30])[C:24]=2[CH:23]=1.[BH4-].[Na+].[Na+].[Cl-]>C1(C)C=CC=CC=1.CO.C1COCC1.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:34]=[CH:33][C:25]4[O:26][C:27]([CH3:31])([CH3:32])[O:28][C:29](=[O:30])[C:24]=4[CH:23]=3)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

9

Reactant 4

HCID 5234Sodium ChlorideHCID 4311764Sodium borohydrideHCID 113345124-[2-(4-Butylphenyl)ethynyl]benzaldehydeHCID 116153306-Amino-2,2-dimethyl-benzo[1,3]dioxin-4-one

Product 1

HCID 114761686-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-oneYield 78%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-[(4-butylphenyl)ethynyl]benzaldehyde (5.43 g, 20.7 mmol, intermediate which may be obtained according to methods disclosed in EP03103780.7) and 6-amino-2,2-dimethyl-4H-1,3-benzodioxin-4-one (4.00 g, 20.7 mmol) in toluene (60 mL) was heated at reflux for 3.5 hours with azeotropic removal of water. Then the mixture was cooled down to 0° C. and anhydrous THF (60 mL) and MeOH (60 1L) were added NaBH4 (1.65 g, 43.6 mmol) was added portionwise and the reaction mixture was stirred for 30 min at 0° C. and 45 min at rt. The reaction mixture was poured into a saturated solution of NaCl and extracted with Et2O. The combined organic layers were dried over MgSO4 and the solvents were removed under reduced pressure to give the crude product. Precipitation from a mixture of EtOAc/MeOH gave 7.1 g (75%) of the title compound as a yellow powder. HPLC, Rt: 5.4 min (purity: 97.5%). 1H NMR (CDCl3) δ: 7.45 (d, J=8.3 Hz, 2H), 7.39 (d, J=8.3 Hz, 2H), 7.28 (d, J=8.3 Hz, 2H), 7.15-7.06 (m, 3H), 6.80-6.70 (m, 2H), 4.20 (m, 2H), 4.04 (brs, 1H), 2.57 (t, J=7.7 Hz, 2H), 1.65 (s, 6H), 1.61-1.49 (m, 2H), 1.37-1.23 (m, 2H), 0.88 (t, J=7.3 Hz, 3H).

Workup

  1. additionwas added portionwise
  2. extractionextracted with Et2O
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. customthe solvents were removed under reduced pressure
  5. customto give the crude product
  6. customPrecipitation
  7. additionfrom a mixture of EtOAc/MeOH

Sources & evidence

ORD record
ord-9930f1739ee4430cb3e5a3b083b12609
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Linked notes

Loading…