Sodium hydride → diethyl 1-{(2R)-1-[(tert-butoxycarbonyl)amino]propan-2-yl}-1H-indole-2,6-dicarboxylate

HRID 1748248Notes

Reaction equation

HRID 1748248 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=2)[CH:5]=[C:4]1[C:17]([O:19][CH2:20][CH3:21])=[O:18].[CH3:22][C@@H:23]1OS(=O)(=O)[N:25]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:24]1>CN(C=O)C>[C:33]([O:32][C:30]([NH:25][CH2:24][C@H:23]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=2)[CH:5]=[C:4]1[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH3:22])=[O:31])([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11195739(s)-Tert-butyl 5-methyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxideHCID 44754779Diethyl 1H-indole-2,6-dicarboxylate2×

Product 1

HCID 67235704diethyl 1-{(2R)-1-[(tert-butoxycarbonyl)amino]propan-2-yl}-1H-indole-2,6-dicarboxylateYield 76.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A stirred suspension of 60% NaH (371 mg, 9.3 mmol) in DMF (10 mL) is cooled in an ice bath, and a solution of diethyl 1H-indole-2,6-dicarboxylate (Intermediate A, 2.6 g, 10.1 mmol) in DMF (10 mL) is added. The mixture is stirred for 20 min, then a solution of tert-butyl (5S)-5-methyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (2.0 g, 8.4 mmol) in DMF (10 mL) is added. The reaction mixture is stirred for 30 min at 0° C. and then warmed to room temperature and stirred for 48 h. The reaction is poured into ice water and the resultant solid is removed by filtration. The filtrate is acidified to pH 3 with 1N aqueous HCl and extracted with EtOAc. The combined extracts are washed with water, brine, dried (Na2SO4) and concentrated to afford the title compound (2.7 g, crude) as an oil.

Workup

  1. temperatureis cooled in an ice bath
  2. stirringThe reaction mixture is stirred for 30 min at 0° C.
  3. stirringstirred for 48 h
  4. customthe resultant solid is removed by filtration
  5. extractionextracted with EtOAc
  6. washThe combined extracts are washed with water, brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6b99260e1a564e6199bf773a227fc2bf
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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