Ethyl Glycolate → Ethyl({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}oxy)acetate

HRID 1512807Notes

Reaction equation

HRID 1512807 reaction equation
[OH:1][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].CC1C=CC(S(O[CH2:21][CH2:22][C:23]2[C:31]3[C:26](=[C:27]([C:32]4[N:36]=[C:35]([C:37]5[CH:42]=[CH:41][C:40]([O:43][CH:44]([CH3:46])[CH3:45])=[C:39]([Cl:47])[CH:38]=5)[O:34][N:33]=4)[CH:28]=[CH:29][CH:30]=3)[N:25]([CH3:48])[CH:24]=2)(=O)=O)=CC=1>CN(C=O)C>[Cl:47][C:39]1[CH:38]=[C:37]([C:35]2[O:34][N:33]=[C:32]([C:27]3[CH:28]=[CH:29][CH:30]=[C:31]4[C:26]=3[N:25]([CH3:48])[CH:24]=[C:23]4[CH2:22][CH2:21][O:1][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4])[N:36]=2)[CH:42]=[CH:41][C:40]=1[O:43][CH:44]([CH3:45])[CH3:46]

Participants

5

Reactant 3

HCID 12184Ethyl GlycolateHCID 24758Sodium hydrideHCID 591460252-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl 4-methylbenzenesulfonate

Product 1

HCID 59146091Ethyl({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}oxy)acetateYield 136.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

To a stirred solution of ethyl hydroxyacetate (23 mg) in DMF (5 mL) was added NaH (18 mg). The reaction mixture was stirred at 20° C. for 15 mins. Then a solution of 2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl 4-methylbenzenesulfonate (D127) (25 mg) in DMF was added dropwise. The mixture was stirred at room temperature for 24 h. The reaction was quenched with water, partitioned between ethyl acetate (25 mL) and water (25 mL). The organic phase was washed with water, 2 M hydrochloric acid and brine, dried over sodium sulphate and evaporated to give the crude product ethyl ({2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}oxy)acetate (D104) (30 mg), used directly in the next step. MS (ES): C26H28ClN3O5 requires 497; found 498.2 (M+H+).

Workup

  1. stirringThe mixture was stirred at room temperature for 24 h
  2. customThe reaction was quenched with water
  3. custompartitioned between ethyl acetate (25 mL) and water (25 mL)
  4. washThe organic phase was washed with water, 2 M hydrochloric acid and brine
  5. dry with materialdried over sodium sulphate
  6. customevaporated

Sources & evidence

ORD record
ord-69e4b4a6f47b4f3caec925864f84cf5b
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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