Ethyl Thioglycolate → (R)-ethyl 2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetate

HRID 920149Notes

Reaction equation

HRID 920149 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C@:8]2([CH3:26])[CH2:12]OS(=O)(=O)[N:9]2[CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=2[O:24][CH3:25])[CH:7]=1.[C:28]([O:32][CH2:33][CH3:34])(=[O:31])[CH2:29][SH:30].CN(C)C(N(C)C)=N>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C@:8]([NH:9][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=2[O:24][CH3:25])([CH3:26])[CH2:12][S:30][CH2:29][C:28]([O:32][CH2:33][CH3:34])=[O:31])[CH:7]=1

Participants

5

Reactant 3

HCID 12185Ethyl ThioglycolateHCID 664601,1,3,3-TetramethylguanidineHCID 90016409(R)-4-(5-bromo-2-fluoro-phenyl)-3-(2,4-dimethoxy-benzyl)-4-methyl-[1,2,3]oxathiazolidine 2,2-dioxide

Product 1

HCID 90067082(R)-ethyl 2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetateYield 100.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of (R)-4-(5-bromo-2-fluoro-phenyl)-3-(2,4-dimethoxy-benzyl)-4-methyl-[1,2,3]oxathiazolidine 2,2-dioxide (10 g, 21.7 mmol, Eq: 1.00) and ethyl thioglycolate (3.92 g, 3.57 ml, 32.6 mmol, Eq: 1.5) in DMF (134 ml) was added at 23° C. 1,1,3,3-tetramethylguanidine (3.75 g, 4.09 ml, 32.6 mmol, Eq: 1.5). The reaction mixture was stirred at 23° C. for 16 hours. The solution was evaporated at HV. The resulting residue was stirred vigorously overnight between 100 ml of dichloromethane and 20% (v/v) sulfuric acid solution (100 ml). Sat. NaHCO3-solution was slowly added (pH=8), then extracted with dichloromethane twice. The combined organic layers were dried over Na2SO4, filtered and evaporated to give the crude product (14.4 g, 132%). The residue was chromatographed on 70 g silica gel with 0-50% ethyl acetate in heptane to give the (R)-ethyl 2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetate (10.9 g, 21.8 mmol, 100% yield) as a light yellow oil. MS (ISP): m/z=500.2 [M+H]+ and 502.2 [M+2+H]+.

Workup

  1. customThe solution was evaporated at HV
  2. stirringThe resulting residue was stirred vigorously overnight between 100 ml of dichloromethane and 20% (v/v) sulfuric acid solution (100 ml)
  3. additionSat. NaHCO3-solution was slowly added (pH=8)
  4. extractionextracted with dichloromethane twice
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude product (14.4 g, 132%)
  9. customThe residue was chromatographed on 70 g silica gel with 0-50% ethyl acetate in heptane

Sources & evidence

ORD record
ord-7986f202bd85494bac11373d202cafa3
Source dataset
uspto-grants-2016_03
Patent number
US09273042B2

Reaction notes

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