Thioglycolic Acid → Tert-butyl 3-{4-[({2',6'-dimethyl-4'-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)amino]-2-fluorophenyl}propanoate

HRID 508072Notes

Reaction equation

HRID 508072 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:5]=[C:4]([CH3:17])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][N:25](S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[C:28]([F:41])[CH:27]=2)[CH:19]=1.SCC(O)=O.O.[OH-].[Li+]>CN(C)C=O>[CH3:17][C:4]1[CH:5]=[C:6]([O:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:7]=[C:2]([CH3:1])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])=[C:28]([F:41])[CH:27]=2)[CH:19]=1

Participants

5

Reactant 3

HCID 1133Thioglycolic AcidHCID 168937Lithium hydroxide, monohydrateHCID 23157466Tert-butyl 3-(4-{({2',6'-dimethyl-4'-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}-2-fluorophenyl)propanoate

Product 1

HCID 23157580Tert-butyl 3-{4-[({2',6'-dimethyl-4'-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)amino]-2-fluorophenyl}propanoateYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl 3-(4-{({2′,6′-dimethyl-4′-[2-(2-oxopyrrolidin-1-yl)ethoxy]biphenyl-3-yl}methyl)[(2-nitrophenyl)sulfonyl]amino}-2-fluorophenyl)propanoate (0.91 g, 1.23 mmol) and mercaptoacetic acid (0.26 mL, 3.68 mmol) in N,N-dimethylformamide (9 mL) was added lithium hydroxide monohydrate (0.31 g, 7.38 mmol) under stirring at room temperature, and the mixture was stirred at the same temperature for 4 hr. The reaction mixture was concentrated under reduced pressure, and to the residue was added brine. The mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate-=5/1-ethyl acetate) to give the title compound (0.51 g, yield 74%) as a colorless amorphous powder.

Workup

  1. stirringthe mixture was stirred at the same temperature for 4 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionto the residue was added brine
  4. extractionThe mixture was extracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate-=5/1-ethyl acetate)

Sources & evidence

ORD record
ord-553a023231b0467e8f9528eedb32e999
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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