Methyl iodide → 7-t-Butyl-5-[(4-methoxy-phenyl)-amino]-3,3,6-trimethyl-2,3-dihydro-benzofuran

HRID 2290152Notes

Reaction equation

HRID 2290152 reaction equation
[CH:1]([C:4]1[C:12]2[O:11][CH2:10][C:9]([CH3:14])([CH3:13])[C:8]=2[CH:7]=[C:6]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:5]=1[CH3:24])([CH3:3])[CH3:2].[CH2:25]([Li])CCC.IC.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[C:1]([C:4]1[C:12]2[O:11][CH2:10][C:9]([CH3:13])([CH3:14])[C:8]=2[CH:7]=[C:6]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:5]=1[CH3:24])([CH3:25])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 186991997-Isopropyl-5-[(4-methoxy-phenyl)-amino]-3,3,6-trimethyl-2,3-dihydro-benzofuran2×HCID 178418339Butyllithium

Product 1

HCID 186991917-t-Butyl-5-[(4-methoxy-phenyl)-amino]-3,3,6-trimethyl-2,3-dihydro-benzofuranYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A stirred solution of 7-isopropyl-5-[(4-methoxy-phenyl)-amino]-3,3,6-trimethyl-2,3-dihydro-benzofuran (Compound 52, 0.2 g, 0.615 mmol) in 5 mL of anhydrous tetrahydrofuran under argon, was cooled to -78° C. and treated with 1.6M solution of n-butyllithium in hexanes (0.77 mL, 1.23 mmol). The resulting green reaction mixture was stirred for 0.5 hour at -78° C. and then treated drop wise with iodomethane (0.5 mL, 6.15 mmol) that was passed through a bed of potassium carbonate. The yellow reaction mixture was allowed to warm to room temperature, recooled to 0° C., quenched with saturated ammonium chloride solution and extracted with diethylether. The organic extract was dried over anhydrous sodium sulfate, filtered and evaporated to a residue which was subjected to flash column chromatography to afford the title compound (0.11 5 g, 51%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3): δ 6.80 (d, 2H, J=9.1 Hz), 6.74 (s, 1H), 6.45 (d, 2H, J=9.1 Hz), 4.24 (s, 2H), 3.77 (s, 3H), 3.60 (br m, 2H), 3.25 (heptet, 1H, J=7.0 Hz), 2.12 (s, 3H), 1.38 (d, 6H, J=7.0 Hz), 1.32 (s, 6H), 1.24 (t, 6H, J=7.0 Hz).

Workup

  1. temperatureto warm to room temperature
  2. customrecooled to 0° C.
  3. customquenched with saturated ammonium chloride solution
  4. extractionextracted with diethylether
  5. extractionThe organic extract
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated to a residue which

Sources & evidence

ORD record
ord-ac425189d4b94aa2a447c940ca10ac38
Source dataset
uspto-grants-2000_07
Patent number
US06093838

Reaction notes

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