Sodium hydride → HCID 90792305, compound

HRID 913053Notes

Reaction equation

HRID 913053 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[NH:15][C:14]([CH:16]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25](=[O:28])[CH2:26][CH3:27])[C:17]([OH:19])=[O:18])=[N:13][CH:12]=1.[H-].[Na+].[CH3:31][Si:32]([CH2:35][CH2:36][O:37][CH2:38]Cl)([CH3:34])[CH3:33]>C1COCC1>[CH2:26]([C:25]1([CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH:16]([C:14]2[N:15]([CH2:38][O:37][CH2:36][CH2:35][Si:32]([CH3:34])([CH3:33])[CH3:31])[C:11]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)=[CH:12][N:13]=2)[C:17]([O:19][C:2]([CH3:11])([CH3:3])[CH3:1])=[O:18])[O:18][CH2:17][CH2:16][O:28]1)[CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 23658521HCID 23658521, compound

Product 1

HCID 90792305HCID 90792305, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 1, A3 in dry THF (0.06 M solution) at 0° C. was added NaH (60%, 1.5 eq.) portionwise, the resulting mixture was stirred for 1 hr and then SEM-Cl (1.5 eq.) was added dropwise. The solution was allowed to warm to RT and stirred for a further 3 hrs. The reaction was quenched by the addition of sat. aq. NH4Cl solution and the mixture extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The crude was purified by column chromatography on silica gel eluting with 20-50% EtOAc/petroleum ether to obtain D1 as a pale brown foam. 1H NMR (400 MHz, CDCl3) δ: 8.32 (1H, s), 7.91-7.75 (5H, m), 7.49-7.37 (2H, m), 5.43 (1H, d, J=10.9 Hz), 5.26 (1H, d, J=10.9 Hz), 3.90 (4H, s), 3.86 (2H, t, J=7.4 Hz), 3.57 (1H, t, J=8.1 Hz), 2.27-2.14 (2H, m), 1.67-1.57 (4H, m), 1.49 (9H, s), 1.41-1.27 (6H, m), 0.96 (2H, t, J=7.4 Hz), 0.87 (3H, t, J=7.5 Hz), 0.07 (9H, s). MS (ES) C35H52N2O5Si requires: 608, found: 609 (M+H)+.

Workup

  1. stirringstirred for a further 3 hrs
  2. customThe reaction was quenched by the addition of sat. aq. NH4Cl solution
  3. extractionthe mixture extracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe crude was purified by column chromatography on silica gel eluting with 20-50% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-4a544688b38e4cee8b412c4427895da6
Source dataset
uspto-grants-2011_09
Patent number
US08026265B2

Reaction notes

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