Cuminaldehyde → HCID 86612368, compound

HRID 1787376Notes

Reaction equation

HRID 1787376 reaction equation
Br[C:2]1[C:10]2[O:9][C:8]([CH3:12])([CH3:11])[CH2:7][C:6]=2[C:5]([CH3:13])=[C:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:3]=1[CH3:22].C([Li])CCC.[CH:28]([C:31]1[CH:38]=[CH:37][C:34]([CH:35]=[O:36])=[CH:33][CH:32]=1)([CH3:30])[CH3:29].O>C1COCC1>[OH:36][CH:35]([C:34]1[CH:37]=[CH:38][C:31]([CH:28]([CH3:30])[CH3:29])=[CH:32][CH:33]=1)[C:2]1[C:10]2[O:9][C:8]([CH3:12])([CH3:11])[CH2:7][C:6]=2[C:5]([CH3:13])=[C:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:3]=1[CH3:22]

Participants

6

Reactant 4

HCID 326CuminaldehydeHCID 962WaterHCID 86612369HCID 86612369, compoundHCID 178418339Butyllithium

Product 1

HCID 86612368HCID 86612368, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl (7-bromo-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl) carbamate (1.77 g, 4.78 mmol) obtained in Example 238 in THF (20 mL) was added dropwise at −78° C. under argon atmosphere n-butyllithium (1.60 M hexane solution, 6.25 mL, 10.0 mmol), and the mixture was stirred for 30 minutes. To the reaction solution was added dropwise at −78° C. a solution of 4-isopropylbenzaldehyde (815 mg, 5.50 mmol) in THF (5 mL). The reaction solution was warmed to room temperature and stirred for 1 hour. Water was added to the reaction solution and the product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4) to obtain 1.20 g (yield: 59%) of tert-butyl (7-(hydroxy(4-isopropylphenyl)methyl)-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)carbamate. To a mixture of the compound (1.00 g, 2.27 mmol) in trifluoroacetic acid (5 mL) was added with ice-cooling triethylsilane (1.0 mL, 6.4 mmol), and the mixture was stirred at room temperature for 1 hour. After the reaction solution was concentrated under reduced pressure, to the residue was added an aqueous saturated sodium hydrogen carbonate solution and the aqueous layer was made alkaline, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product of 7-(4-isopropylbenzyl)-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-amine. To a solution of the compound (330 mg, about 1.02 mmol) and tert-butylacetyl chloride (0.16 mL, 1.12 mmol) in dichloromethane (30 mL) was added triethylamine (0.16 mL, 1.12 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, the organic layer was separated, and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with 1 N hydrochloric acid and an aqueous saturated sodium hydrogen carbonate solution, dried over magnesium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain 273 mg (yield: 17%) of the title compound. Melting point: 170-171° C. (ethyl acetate-hexane).

Workup

  1. stirringstirred for 1 hour
  2. extractionthe product was extracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-f798a01a9497439baa1ca3c2091e0bfb
Source dataset
uspto-grants-2009_03
Patent number
US07507841B2

Reaction notes

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