Acetic Acid → 5-(1-isopropyl-piperidin-4-yl)-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 513862Notes

Reaction equation

HRID 513862 reaction equation
Cl.[CH2:2]([O:4][C:5]([C:7]1[N:8]([S:22]([C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:24])=[O:23])[C:9]2[C:14]([CH:15]=1)=[CH:13][C:12]([CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[CH:11][CH:10]=2)=[O:6])[CH3:3].C(N(CC)CC)C.[CH3:39][C:40]([CH3:42])=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[CH2:2]([O:4][C:5]([C:7]1[N:8]([S:22]([C:25]2[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=2)(=[O:23])=[O:24])[C:9]2[C:14]([CH:15]=1)=[CH:13][C:12]([CH:16]1[CH2:21][CH2:20][N:19]([CH:40]([CH3:42])[CH3:39])[CH2:18][CH2:17]1)=[CH:11][CH:10]=2)=[O:6])[CH3:3]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 180AcetoneHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 680052465-piperidin-4-yl-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester hydrochloride

Product 1

HCID 680052175-(1-isopropyl-piperidin-4-yl)-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 5-piperidin-4-yl-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester hydrochloride (253 mg, 0.592 mmol) in dichloroethane (4 ml), triethylamine (0.17 ml, 1.18 mmol), acetone (1.44 ml, 19.6 mmol), acetic acid (0.28 ml, 4.89 mmol), and sodium triacetoxyborohydride (318 mg, 1.50 mmol) was stirred at room temperature for 14.5 hours. The pH of the reaction mixture was adjusted to 9 (basic) using an aqueous solution saturated with sodium bicarbonate. The mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution saturated with sodium chloride, and then dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and concentration was performed. The resulting residue was purified by amino gel column chromatography (hexane/ethyl acetate=92/8 to 35/65). Thus, 5-(1-isopropyl-piperidin-4-yl)-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester was obtained as a colorless gum-like material (191 mg, 69%).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe extract was washed with an aqueous solution saturated with sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe desiccant was removed by filtration, and concentration
  5. customThe resulting residue was purified by amino gel column chromatography (hexane/ethyl acetate=92/8 to 35/65)

Sources & evidence

ORD record
ord-469bcd8972cb42c7ba985c24c6b3d54e
Source dataset
uspto-grants-2015_08
Patent number
US09102692B2

Reaction notes

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