O,O-Dipyridin-2-yl carbonothioate → 1-t-Butoxycarbonyl-2,3-dihydro-4-isothiocyanato-7-methylindole

HRID 1275670Notes

Reaction equation

HRID 1275670 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([NH2:18])[CH:13]=[CH:14][C:15]=2[CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=C(O[C:26](OC2N=CC=CC=2)=[S:27])N=CC=1>C(Cl)Cl.CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([N:18]=[C:26]=[S:27])[CH:13]=[CH:14][C:15]=2[CH3:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 719784O,O-Dipyridin-2-yl carbonothioateHCID 224612391-t-Butoxycarbonyl-4-amino-2,3-dihydro-7-methylindole

Product 1

HCID 224612381-t-Butoxycarbonyl-2,3-dihydro-4-isothiocyanato-7-methylindoleYield 94%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

1-t-Butoxycarbonyl-4-amino-2,3-dihydro-7-methylindole (1.625 g, 6.55 mmol) is dissolved in methylene chloride (15 mL). To this solution is added 4-dimethylaminopyridine (0.160 g, 1.31 mmol) and di-2-pyridyl thionocarbonate (1.52 g, 6.55 mmol). The volume of solvent is brought to 30 mL, and the solution is allowed to stir for one hour. The solution is diluted to 150 mL with chloroform and washed first with four 75-mL portions of aqueous citric acid solution followed by three 100-mL portions of aqueous potassium carbonate. The organic layer is dried over anhydrous potassium carbonate, filtered and the solvent is removed by rotary evaporation to yield an orange, oily solid. The crude product is purified by silica gel flash column chromatography using 4% ethyl acetate/hexanes to afford 1.78 g of N-t-butoxycarbonyl-2,3-dihydro-4-isothiocyanato-7-methylindole as a white solid (94% yield).

Workup

  1. washwashed first with four 75-mL portions of aqueous citric acid solution
  2. dry with materialThe organic layer is dried over anhydrous potassium carbonate
  3. filtrationfiltered
  4. customthe solvent is removed by rotary evaporation
  5. customto yield an orange, oily solid
  6. customThe crude product is purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-4ef249ff203e40f98c32a6d2a013cb4c
Source dataset
uspto-grants-2000_12
Patent number
US06162818

Reaction notes

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