Tert-Butylamine → HCID 68706202, compound

HRID 2376434Notes

Reaction equation

HRID 2376434 reaction equation
ClC(OCC(Cl)(Cl)Cl)=O.C(N(CC)CC)C.ClC(Cl)(Cl)C[O:20][C:21](=O)[NH:22][C:23]1[C:24]([CH3:42])=[CH:25][C:26]2[O:30][CH2:29][CH:28]([C:31]3[CH:36]=[CH:35][C:34]([CH:37]([CH3:39])[CH3:38])=[CH:33][CH:32]=3)[C:27]=2[C:40]=1[CH3:41].[C:46]([NH2:50])([CH3:49])([CH3:48])[CH3:47]>CS(C)=O.O>[C:46]([NH:50][C:21]([NH:22][C:23]1[C:24]([CH3:42])=[CH:25][C:26]2[O:30][CH2:29][C@H:28]([C:31]3[CH:32]=[CH:33][C:34]([CH:37]([CH3:39])[CH3:38])=[CH:35][CH:36]=3)[C:27]=2[C:40]=1[CH3:41])=[O:20])([CH3:49])([CH3:48])[CH3:47]

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 8471TriethylamineHCID 870632,2,2-Trichloroethyl chloroformateHCID 86618057HCID 86618057, compound

Product 1

HCID 68706202HCID 68706202, compoundYield 89.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Procedure

To a solution of (+)-(3R)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-amine (1.0 g, 3.55 mmol) obtained in Reference Example 141 in THF (10 mL) was added dropwise with ice-cooling 2,2,2-trichloroethyl chloroformate (0.49 mL, 3.55 mmol), was added triethylamine (0.52 mL, 3.73 mmol) and the reaction mixture was stirred for 30 minutes, and then the reaction solution was warmed to room temperature. Water was added to the reaction solution, and the product was extracted with ethyl acetate. The organic layer was washed with water, an aqueous saturated sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate, filtered, and then concentrated under reduced pressure. The solution of the obtained 2,2,2-trichloroethyl(3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)carbamate (1.60 g, 3.50 mmol) and tert-butylamine (779 mg, 10.65 mmol) in dimethylsulfoxide (20 mL) was stirred at 45° C. for 5 hours under an argon atmosphere. Water was added to the reaction solution, and the product was extracted with ethyl acetate. The organic layer was washed with water, an aqueous saturated sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane ethyl acetate=2:1) to obtain 1.19 g (yield: 88%) of the title compound. Melting point: 205-206° C. (ethyl acetate-hexane). [α]D20=+81.0° (c=0.51, chloroform).

Workup

  1. additionwas added dropwise with ice-
  2. extractionthe product was extracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialan aqueous saturated sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. extractionthe product was extracted with ethyl acetate
  8. washThe organic layer was washed with water
  9. dry with materialan aqueous saturated sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (hexane ethyl acetate=2:1)

Sources & evidence

ORD record
ord-97b87f202d4d4e5a8fbf6b3978e00572
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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