Tetrahydrofuran → 4-tert-butyl 1-methyl 2-(4-(tert-butoxycarbonylamino)-1H-indol-1-yl)-2-(4-chlorophenyl)succinate

HRID 1477909Notes

Reaction equation

HRID 1477909 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=N[N:13]2[CH:18]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)[C:19]([O:21][CH3:22])=[O:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].[H-].[Na+].[CH2:41]1COCC1>>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:41][N:13]2[C:18]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)([CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:19]([O:21][CH3:22])=[O:20])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 70563540methyl 2-(4-(tert-butoxycarbonylamino)-1H-indazol-1-yl)-2-(4-chlorophenyl)acetate

Product 1

HCID 705860914-tert-butyl 1-methyl 2-(4-(tert-butoxycarbonylamino)-1H-indol-1-yl)-2-(4-chlorophenyl)succinate

Procedure

A solution of methyl 2-(4-(tert-butoxycarbonylamino)-1H-indazol-1-yl)-2-(4-chlorophenyl)acetate (2 g, 4.83 mmol), as described in Example 2 Step B, and tert-butyl 2-bromoacetate (1.4 g, 7.25 mmol) in THF (10 mL) was added to NaH (290 mg, 7.25 mmol, 60% in oil) dropwise at 0° C. and stirred for 30 min. The mixture was quenched with saturated NH4Cl solution, and extracted with ethyl acetate. The organic layer was washed with brine (20 mL), dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography (PE:EA=3:1) to afford the title compound. LC/MS m/z=529.2[M+H]+.

Workup

  1. customThe mixture was quenched with saturated NH4Cl solution
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography (PE:EA=3:1)

Sources & evidence

ORD record
ord-053e2d6ebdce48dfb74e8c2e39fbfb79
Source dataset
uspto-grants-2016_08
Patent number
US09403807B2

Reaction notes

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