Sodium hydride → 1H-Indole-2,6-dicarboxylic acid, 1-[(1S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-methylpropyl]-, 2,6-diethyl ester

HRID 1748279Notes

Reaction equation

HRID 1748279 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:26]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:25][CH2:24]1.[NH4+].[Cl-]>CN(C=O)C.O.CCCCCC>[C:34]([O:33][C:31]([NH:26][CH2:25][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:32])([CH3:37])([CH3:36])[CH3:35]

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 44754779Diethyl 1H-indole-2,6-dicarboxylateHCID 86682391HCID 86682391, compound

Product 1

HCID 672355501H-Indole-2,6-dicarboxylic acid, 1-[(1S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-1-methylpropyl]-, 2,6-diethyl esterYield 121.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of hexane washed 60% sodium hydride in mineral oil (91 mg, 2.3 mmol) in DMF (2.5 mL) under nitrogen atmosphere to 0° C. is added a solution of diethyl 1H-indole-2,6-dicarboxylate (619 mg, 2.4 mmol) in DMF (4 mL). The mixture is stirred for 20 min at 0° C. and a solution of tert-butyl (6R)-6-methyl-1,2,3-oxathiazinane-3-carboxylate 2,2-dioxide (518 mg, 2.1 mmol) in DMF (2.5 mL) is added. The reaction mixture is stirred for 30 min at 0° C. and is warmed to room temperature and stirred for 72 h. Water and NH4Cl solution are added and the mixture is stirred for 15 min. The aqueous mixture is extracted with EtOAc (50 mL) and the organic layer is washed with water, brine, dried (MgSO4) and concentrated to afford the title crude compound (1.1 g) which is used in the next step without purification.

Workup

  1. stirringThe reaction mixture is stirred for 30 min at 0° C.
  2. temperatureis warmed to room temperature
  3. stirringstirred for 72 h
  4. stirringthe mixture is stirred for 15 min
  5. extractionThe aqueous mixture is extracted with EtOAc (50 mL)
  6. washthe organic layer is washed with water, brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-6dc63b12e6694a80991d1b27d02fde3c
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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