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

HRID 1809510Notes

Reaction equation

HRID 1809510 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 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Prepared using General Procedure 9. To a flame-dried flask under N2 was added (R)-tert-butyl 4-cyano-2,3-dihydro-1H-inden-1-ylcarbamate INT-8 (8.3 g, 32.1 mmol) in anhydrous DMF (240 mL). The reaction mixture was cooled to 0° C. and sodium hydride (3.8 g, 60% in oil, 160.6 mmol) was added portionwise. After stirring at 0° C. for 2.75 h, (2-bromoethoxy)(tert-butyl)dimethylsilane (16.9 mL, 70.7 mmol) was added. The ice bath was removed after 5 mins and the reaction mixture was allowed to warm to room temperature. After 1.5 h, the reaction mixture was quenched by the slow addition of sat. NaHCO3 at 0° C. Once gas evolution was complete the reaction was extracted with EA. The organic layers were washed with water and brine, dried over MgSO4 and concentrated. The product was purified by chromatography (EA/hexanes) to provide 10.76 g (80%) of (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate INT-16 as a colorless oil. LCMS-ESI (m/z) calculated for C23H36N2O3Si: 416.6; found 317.2 [M-Boc]+ and 439.0 [M+Na]+, tR=4.04 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J=7.6, 1H), 7.38-7.32 (m, 1H), 7.33-7.18 (m, 1H), 5.69 (s, 0.5H), 5.19 (s, 0.5H), 3.70 (ddd, J=48.8, 26.6, 22.9, 1.5H), 3.50-3.37 (m, 1H), 3.17 (ddd, J=16.7, 9.4, 2.2, 2H), 2.93 (m, 1.5H), 2.45 (s, 1H), 2.21 (dd, J=24.5, 14.5, 1H), 1.56-1.37 (bs, 4.5H), 1.22 (bs, 4.5H), 0.87-0.74 (m, 9H), −0.04 (dd, J=26.6, 8.2, 6H). 13C NMR (101 MHz, CDCl3) δ 155.03, 146.55, 145.54, 131.16, 130.76, [128.11, 127.03], 117.58, 109.20, 79.88, [63.93, 61.88], [61.44, 60.34], [49.73, 46.76], 30.30, 29.70, 28.44, 28.12, [25.87, 25.62], −5.43. (S)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate INT-17 is prepared in an analogous fashion using INT-9.

Workup

  1. customPrepared
  2. customThe ice bath was removed after 5 mins
  3. temperatureto warm to room temperature
  4. waitAfter 1.5 h
  5. customthe reaction mixture was quenched by the slow addition of sat. NaHCO3 at 0° C
  6. extractionwas extracted with EA
  7. washThe organic layers were washed with water and brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe product was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-a5f7de562d8b4b3b925825305296e24f
Source dataset
uspto-grants-2013_01
Patent number
US08362048B2

Reaction notes

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