Sodium Carbonate → 3-[3-tert-Butylsulfanyl-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

HRID 2366087Notes

Reaction equation

HRID 2366087 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17]N)=[CH:13][CH:12]=1.[CH2:19]([O:21][C:22](=[O:35])[C:23]([CH3:34])([CH3:33])[CH2:24][C:25](=O)[CH2:26][S:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH3:20].CC([O-])=O.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CC(O)=O.O>[CH2:19]([O:21][C:22](=[O:35])[C:23]([CH3:34])([CH3:33])[CH2:24][C:25]1[NH:17][C:14]2[C:15]([C:26]=1[S:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:16][C:11]([O:10][CH2:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][N:3]=1)=[CH:12][CH:13]=2)[CH3:20]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 517045Sodium AcetateHCID 3576811Ethyl 5-(tert-butylsulfanyl)-2,2-dimethyl-4-oxopentanoate3×HCID 44474905[4-(Pyridin-2-ylmethoxy)-phenyl]-hydrazine dihydrochloride

Product 1

HCID 444749063-[3-tert-Butylsulfanyl-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl esterYield 62.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

[4-(Pyridin-2-ylmethoxy)-phenyl]-hydrazine dihydrochloride (75 g), 5-tert-butylsulfanyl-2,2-dimethyl-4-oxo-pentanoic acid ethyl ester (64 g), NaOAc (40 g) in toluene (800 mL) and HOAc (400 mL) was stirred at room temperature for 3 days. In one aspect, 5-tert-butylsulfanyl-2,2-dimethyl-4-oxo-pentanoic acid ethyl ester was prepared according to the procedures described in U.S. Pat. No. 5,288,743 issued Feb. 22, 1994. In another aspect, 5-tert-butylsulfanyl-2,2-dimethyl-4-oxo-pentanoic acid ethyl ester was prepared as outlined herein. The mixture was poured into water and made basic with solid Na2CO3. The mixture was extracted with EtOAc (×3), then washed with water (×2), brine, dried (MgSO4), filtered and concentrated to give a dark red-black oil. Column chromatography of the mother liquor (silica gel packed in hexanes; eluting with hexane then hexane-EtOAc 9:1 rising to 4:1) afforded 68 g of the title compound, as a yellow solid.

Workup

  1. extractionThe mixture was extracted with EtOAc (×3)
  2. washwashed with water (×2), brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a dark red-black oil
  7. washeluting with hexane

Sources & evidence

ORD record
ord-0dc21827d19d4551b2916d4e96fb6b38
Source dataset
uspto-grants-2014_04
Patent number
US08697730B2

Reaction notes

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