Hexane → HCID 86612342, compound

HRID 1787110Notes

Reaction equation

HRID 1787110 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:10])[CH3:9])=[CH:4][CH:3]=1.C([Li])CCC.CCCCCC.[CH3:22][C:23]1([CH3:43])[C:27](=[O:28])[C:26]2[CH:29]=[C:30]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:31]([CH3:34])=[C:32]([CH3:33])[C:25]=2[O:24]1>C1COCC1.O>[OH:28][C:27]1([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:10])[CH3:9])=[CH:4][CH:3]=2)[C:26]2[CH:29]=[C:30]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C:31]([CH3:34])=[C:32]([CH3:33])[C:25]=2[O:24][C:23]1([CH3:43])[CH3:22]

Participants

7

Reactant 4

HCID 8058HexaneHCID 114621-Bromo-4-isopropylbenzeneHCID 86612343HCID 86612343, compoundHCID 178418339Butyllithium

Product 1

HCID 86612342HCID 86612342, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-bromocumene (6.25 g, 31.4 mmol) in THF (50 mL) was added dropwise a solution of n-butyllithium in hexane (1.60 M, 19.6 mL, 31.4 mmol) under arogon atmosphere at −78° C., and the mixture was stirred at the same temperature for 30 minutes. Then, to the reaction solution was added dropwise a solution of tert-butyl (2,2,6,7-tetramethyl-3-oxo-2,3-dihydro-1-benzofuran-5-yl)carbamate obtained in Reference Example 59 (500 mg, 2.02 mmol) in THF (5 mL) at the same temperature, and the reaction solution was stirred at room temperature for 1 hour, followed by addition of water, which was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain oily tert-butyl (3-hydroxy-3-(4-isopropylphenyl)-2,2,6,7-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)carbamate. A mixture of said compound with trifluoroacetic acid (10 mL) was added triethylsilane (1.0 mL, 6.4 mmol) with ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and to the residue was added a saturated sodium hydrogen carbonate solution to alkalify the aqueous layer, which was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain the free salt of the title compound. Then, it was made hydrochloride in a 4 N hydrochloric acid/methanol solution to obtain 2.03 g (yield 37%) of the title compound. Melting point: 166-168° C. (decomp.) (methanol).

Workup

  1. stirringthe reaction solution was stirred at room temperature for 1 hour
  2. extractionwas 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 residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1)

Sources & evidence

ORD record
ord-d56a2f205fb14ed195d7ae398bd709e5
Source dataset
uspto-grants-2009_03
Patent number
US07507841B2

Reaction notes

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