Sodium hydride → Benzyl 1-(tert-butoxycarbonylmethyl)-2-indolecarboxylate

HRID 844430Notes

Reaction equation

HRID 844430 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11].[H-].[Na+].Br[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>CN(C=O)C>[C:27]([O:26][C:24]([CH2:23][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 7723355benzyl 1H-indole-2-carboxylate

Product 1

HCID 22612588Benzyl 1-(tert-butoxycarbonylmethyl)-2-indolecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

50.25 g of benzyl 2-indolecarboxylate (Preparation 2.1, step A) are dissolved in 140 ml of anhydrous DMF, followed by addition over 30 minutes, under a stream of dry nitrogen, of a solution of 6.6 g of NaH at 80% in oil, in 100 ml of DMF. The reaction medium is stirred for 90 minutes at RT and is then cooled on an ice bath and 42.91 ml of tert-butyl bromoacetate are added dropwise. After stirring at RT overnight, the DMF is evaporated off and the residue is taken up in DCM and then in water. After stirring, the phases are separated by settling and the aqueous phase is then extracted twice-with DCM; the combined organic phases are washed with saturated NaCl solution and then dried over MgSO4. After filtration and evaporation, the residue is taken up in a mixture of 100 ml of ethyl ether and 100 ml of heptane. After stirring for 2 hours, the crystals formed are filtered off and then washed with 50 ml of a heptane/ethyl ether mixture (70/30; v/v) and dried in an oven. 58 g of the expected product are obtained: m.p. 95-96° C.

Workup

  1. temperatureis then cooled on an ice bath
  2. stirringAfter stirring at RT overnight
  3. customthe DMF is evaporated off
  4. stirringAfter stirring
  5. customthe phases are separated
  6. extractionthe aqueous phase is then extracted twice-with DCM
  7. washthe combined organic phases are washed with saturated NaCl solution
  8. dry with materialdried over MgSO4
  9. filtrationAfter filtration and evaporation
  10. additionthe residue is taken up in a mixture of 100 ml of ethyl ether and 100 ml of heptane
  11. stirringAfter stirring for 2 hours
  12. customthe crystals formed
  13. filtrationare filtered off
  14. washwashed with 50 ml of a heptane/ethyl ether mixture (70/30; v/v)
  15. customdried in an oven

Sources & evidence

ORD record
ord-fdd2ea3914d04df18b6ae55638cd1530
Source dataset
uspto-grants-2002_04
Patent number
US06380230B1

Reaction notes

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