Sodium hydride → Ethyl 1-(2,2-Diethoxyethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate

HRID 1021890Notes

Reaction equation

HRID 1021890 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]1[C:12]([O:14][CH2:15][CH3:16])=[O:13].Br[CH2:18][CH:19]([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22]>CN(C)C=O>[CH2:21]([O:20][CH:19]([O:23][CH2:24][CH3:25])[CH2:18][N:3]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[C:4]1[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH3:22]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 300702ethyl 4,5,6,7-tetrahydro-1H-indole-2-carboxylate

Product 1

HCID 86683752Ethyl 1-(2,2-Diethoxyethyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (1.44 g, 60.2 mmol) in N,N-dimethylformamide (DMF) (30 mL) was slowly added 195a (5.80 g, 30.1 mmol) at 0° C. The resulting mixture was stirred at room temperature for 0.5 h, followed by the addition of 2-bromo-1,1-diethoxyethane (11.9 g, 60.2 mmol). The reaction was heated at 70° C. for 30 h and quenched with water (100 mL). The mixture was then extracted with ethyl acetate (3×100 mL). The combined organic phase was concentrated under reduced pressure and the residue was purified with silica-gel column chromatography eluting with 40:1 petroleum ether/ethyl acetate to 195b (4.7 g, 51%). MS-ESI: [M-EtOH+H]+ 264. 1H NMR (500 MHz, DMSO-d6) δ 6.65 (s, 1H), 4.59 (t, J=5.0 Hz, 1H), 4.17-4.16 (m, 4H), 3.59-3.57 (m, 2H), 3.27-3.26 (m, 2H), 2.61 (t, J=6.0 Hz, 2H), 2.51 (t, J=6.0 Hz, 2H), 1.73-1.71 (m, 2H), 1.63-1.61 (m, 2H), 1.25 (t, J=7.0 Hz, 3H), 1.02 (t, J=7.0 Hz, 6H).

Workup

  1. temperatureThe reaction was heated at 70° C. for 30 h
  2. customquenched with water (100 mL)
  3. extractionThe mixture was then extracted with ethyl acetate (3×100 mL)
  4. concentrationThe combined organic phase was concentrated under reduced pressure
  5. customthe residue was purified with silica-gel column chromatography
  6. washeluting with 40:1 petroleum ether/ethyl acetate to 195b (4.7 g, 51%)

Sources & evidence

ORD record
ord-93e5e910ca6c4f3e8fabdf78cd661bf3
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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