Sodium hydride → (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate

HRID 1807609Notes

Reaction equation

HRID 1807609 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C@H:7]2[NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])#[N:2].[H-].[Na+].Br[CH2:23][CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]>CN(C=O)C>[Si:26]([O:25][CH2:24][CH2:23][N:12]([C@H:7]1[C:8]2[C:4](=[C:3]([C:1]#[N:2])[CH:11]=[CH:10][CH:9]=2)[CH2:5][CH2:6]1)[C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 52938554(R)-tert-Butyl (4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate

Product 1

HCID 58344554(R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-cyano-2,3-dihydro-1H-inden-1-yl)carbamateYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To (R)-tert-butyl 4-cyano-2,3-dihydro-1H-inden-1-ylcarbamate INT-52 (0.700 g, 2.7 mmol) was added anhydrous DMF (10 mL) and the reaction mixture was stirred in a 0° C. ice bath under N2. Sodium hydride (0.541 g, 13.5 mmol) was added and the mixture was stirred at 0° C. for 2 h. After 2 h, (2-bromoethoxy)-tert-butyldimethylsilane (1.43 g, 5.9 mmol) was added and the reaction mixture was allowed to warm to room temperature for 1 h. The reaction was cooled to 0° C. and quenched with MeOH followed by saturated NaHCO3. The mixture was extracted with EA and brine. The combined organic layers were dried over MgSO4, filtered, and concentrated to produce a brown oil. The crude product was purified by silica gel flash chromatography (20% EA/Hexanes) to afford 0.868 g (77%) of (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate INT-59 as a yellow oil. LCMS-ESI (m/z) calculated for C23H36N2O3Si: 416.6; found 317.1 [M+H−Boc]+, tR=4.05 min. 1H NMR (400 MHz, (CD3)2SO) δ 7.50 (m, 1H), 7.37 (m, 1H), 7.26 (m, 1H), 5.78 (m, 1H), 4.02 (m, 2H), 3.51 (m, 2H), 3.29 (m, 1H), 2.97 (m, 1H), 2.26 (m, 2H), 1.40 (s, 9H), 0.83 (s, 9H), 0.09 (s, 6H).

Workup

  1. stirringthe mixture was stirred at 0° C. for 2 h
  2. temperatureto warm to room temperature for 1 h
  3. temperatureThe reaction was cooled to 0° C.
  4. customquenched with MeOH
  5. extractionThe mixture was extracted with EA and brine
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto produce a brown oil
  10. customThe crude product was purified by silica gel flash chromatography (20% EA/Hexanes)

Sources & evidence

ORD record
ord-55c1bba9a133451181b1bbe54f431155
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

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