Sodium hydride → HCID 67085779, compound

HRID 2036753Notes

Reaction equation

HRID 2036753 reaction equation
[C:1]1([S:7]([C:10]2[CH:18]=[CH:17][C:16]3[NH:15][C:14]4[CH2:19][CH:20]5[NH:24][CH:23]([C:13]=4[C:12]=3[C:11]=2[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22][CH2:21]5)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:35][CH2:36][O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1OCCOCCOCCOCCOCCOC1>[C:1]1([S:7]([C:10]2[CH:18]=[CH:17][C:16]3[N:15]([CH2:35][CH2:36][O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[C:14]4[CH2:19][CH:20]5[NH:24][CH:23]([C:13]=4[C:12]=3[C:11]=2[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22][CH2:21]5)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 67085592HCID 67085592, compound

Product 1

HCID 67085779HCID 67085779, compoundYield 99.3%

Reagents, catalysts & solvents 3

HCID 2855718-Crown-6CatalystHCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of the product of Example 88, step C (120 mg, 0.27 mmol) in anhydrous DMF (3 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 22 mg, 0.54 mmol), tetrabutylammonium iodide (51 mg, 0.13 mmol) and 18-crown-6 (7 mg, 0.02 mmol). The resulting mixture was stirred for 30 min before 2-bromoethoxy-tert-butyldimethylsilane (0.07 ml, 0.32 mmol) was added. The reaction mixture was stirred at room temperature for 4 h, quenched with water and extracted with ethyl acetate. The organic extract was dried over sodium sulfate, filtered, and concentrated to give tert-butyl 2-phenylsulfonyl-5-[2-(tert-butyldimethylsilyloxy)]ethyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate (160 mg, quant) as a yellow-brown solid: 1H NMR (CDCl3, 300 MHz), δ 8.39 (s, 1H), 8.14-8.18 (m, 2H), 7.86 (d, J=8.4 Hz, 1H), 7.63-7.71 (m, 3H), 7.56 (d, J=8.7 Hz, 1H), 5.47 (br s, 1H), 4.91 (br s, 1H), 4.25-4.38 (m, 2H), 4.03 (t, J=5.4 Hz, 2H), 2.76 (d, J=16.2 Hz, 1H), 2.34-2.57 (m, 2H), 2.10-2.22 (m, 1H), 1.79-1.86 (m, 2H), 1.58 (s, 9H), 0.93 (s, 9H), 0.04 (s, 3H), 0.01 (s, 3H).

Workup

  1. additionwas added
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. extractionThe organic extract
  5. dry with materialwas dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-ebb290e0676348c48d5d582f8feae536
Source dataset
uspto-grants-2013_11
Patent number
US08575186B2

Reaction notes

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