Sodium hydride → HCID 131734769, compound

HRID 1777730Notes

Reaction equation

HRID 1777730 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[N:11]=[C:12]([Br:33])[S:13][C:14]=1[N:15]1[CH2:20][CH2:19][N:18]([C:21](=[O:32])[CH2:22][N:23]2[C:27]3=[N:28][CH:29]=[CH:30][CH:31]=[C:26]3[CH:25]=[CH:24]2)[CH2:17][CH2:16]1.[H-].[Na+].[CH3:36][Si:37]([CH2:40][CH2:41][O:42][CH2:43]Cl)([CH3:39])[CH3:38]>C1COCC1>[Br:33][C:12]1[S:13][C:14]([N:15]2[CH2:20][CH2:19][N:18]([C:21](=[O:32])[CH2:22][N:23]3[C:27]4=[N:28][CH:29]=[CH:30][CH:31]=[C:26]4[CH:25]=[CH:24]3)[CH2:17][CH2:16]2)=[C:10]([C:2]2[N:1]([CH2:43][O:42][CH2:41][CH2:40][Si:37]([CH3:39])([CH3:38])[CH3:36])[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[N:11]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 71680471HCID 71680471, compound

Product 1

HCID 131734769HCID 131734769, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a yellow solution of Example 38 (542 mg) in THF (6 mL) was added NaH (62 mg, 60% in mineral oil) at 0° C. The resulting pale yellow foaming suspension was stirred at 0° C. for 15 min under argon, then SEMCl (182 mg) was added and stirring was continued for 1.25 h. The reaction mixture was quenched by addition of water. Phases were separated and the org. layer was washed with water and brine. The aq. layers were extracted twice with EA. The combined org. layers were dried over MgSO4, filtrated off, evaporated and dried in high vacuo. The crude was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in % B: 5 for 4CV, 5 to 15 over 6CV, 15 for 3CV) to afford 530 mg of light yellow solid. LC-MS (B): tR=0.91 min; [M+H]+: 652.48.

Workup

  1. stirringstirring
  2. waitwas continued for 1.25 h
  3. customThe reaction mixture was quenched by addition of water
  4. customPhases were separated
  5. washlayer was washed with water and brine
  6. extractionThe aq. layers were extracted twice with EA
  7. dry with materiallayers were dried over MgSO4
  8. filtrationfiltrated off
  9. customevaporated
  10. customdried in high vacuo
  11. customThe crude was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: DCM; solvent B: DCM/MeOH 8/2; gradient in % B: 5 for 4CV, 5 to 15 over 6CV, 15 for 3CV)
  12. customto afford 530 mg of light yellow solid

Sources & evidence

ORD record
ord-4a4a577e1ccd42a8be96bc8b03fee1ab
Source dataset
uspto-grants-2016_02
Patent number
US09266876B2

Reaction notes

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