Ethanol → SGD 1882

HRID 1429670Notes

Reaction equation

HRID 1429670 reaction equation
[Li+].[BH4-].[NH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH2:11][C@@H:12]3[N:18]([CH:19]=2)[C:17](=[O:20])[C:16]2[CH:21]=[C:22]([O:64][CH3:65])[C:23]([O:25][CH2:26][CH2:27][CH2:28][O:29][C:30]4[C:61]([O:62][CH3:63])=[CH:60][C:33]5[C:34](=[O:59])[N:35]6[CH:50]=[C:49]([C:51]7[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=7)[CH2:48][C@H:36]6[C:37](=O)[N:38](COCC[Si](C)(C)C)[C:32]=5[CH:31]=4)=[CH:24][C:15]=2[N:14](COCC[Si](C)(C)C)[C:13]3=O)=[CH:6][CH:5]=1.CCO>C1COCC1>[NH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH2:11][C@@H:12]3[N:18]([CH:19]=2)[C:17](=[O:20])[C:16]2[CH:21]=[C:22]([O:64][CH3:65])[C:23]([O:25][CH2:26][CH2:27][CH2:28][O:29][C:30]4[C:61]([O:62][CH3:63])=[CH:60][C:33]5[C:34](=[O:59])[N:35]6[CH:50]=[C:49]([C:51]7[CH:52]=[CH:53][C:54]([O:57][CH3:58])=[CH:55][CH:56]=7)[CH2:48][C@H:36]6[CH:37]=[N:38][C:32]=5[CH:31]=4)=[CH:24][C:15]=2[N:14]=[CH:13]3)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 4148881Lithium borohydrideHCID 86656478HCID 86656478, compound

Product 1

HCID 45257190SGD 1882Yield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Fresh LiBH4 (183 mg, 8.42 mmol) was added to a stirred solution of the SEM-dilactam 10 (428 mg, 0.42 mmol) in THF (5 mL) and EtOH (5 mL) at room temperature. After 10 minutes, delayed vigorous effervescence was observed requiring the reaction vessel to be placed in an ice bath. After removal of the ice bath the mixture was allowed to stir at room temperature for 1 hour. LC/MS analysis at this point revealed total consumption of starting material with very little mono-reduced product. The reaction mixture was poured onto ice (100 mL) and allowed to warm to room temperature with stirring. The aqueous mixture was extracted with DCM (3×30 mL) and the combined organic layers washed with H2O (20 mL), brine (30 mL) and concentrated in vacuo. The resulting residue was treated with DCM (5 mL), EtOH (14 mL), H2O (7 mL) and silica gel (10 g). The viscous mixture was allowed to stir at room temperature for 3 days. The mixture was filtered slowly through a sinter funnel and the silica residue washed with 90% CHCl3: 10% MeOH (˜250 mL) until UV activity faded completely from the eluent. The organic phase was washed with H2O (50 mL), brine 60 mL), dried (MgSO4) filtered and evaporated in vacuo to provide the crude material. The crude product was purified by flash chromatography (97% CHCl3: 3% MeOH) to provide the pure C2/C2′ aryl PBD dimer 11 (185 mg) 61% yield.

Workup

  1. customat room temperature
  2. customto be placed in an ice bath
  3. customAfter removal of the ice bath the mixture
  4. customconsumption of starting material with very little mono-reduced product
  5. additionThe reaction mixture was poured onto ice (100 mL)
  6. temperatureto warm to room temperature
  7. stirringwith stirring
  8. extractionThe aqueous mixture was extracted with DCM (3×30 mL)
  9. washthe combined organic layers washed with H2O (20 mL), brine (30 mL)
  10. concentrationconcentrated in vacuo
  11. additionThe resulting residue was treated with DCM (5 mL), EtOH (14 mL), H2O (7 mL) and silica gel (10 g)
  12. stirringto stir at room temperature for 3 days
  13. filtrationThe mixture was filtered slowly through a sinter funnel
  14. washthe silica residue washed with 90% CHCl3
  15. washThe organic phase was washed with H2O (50 mL), brine 60 mL),
  16. dry with materialdried (MgSO4)
  17. filtrationfiltered
  18. customevaporated in vacuo
  19. customto provide the crude material
  20. customThe crude product was purified by flash chromatography (97% CHCl3: 3% MeOH)

Sources & evidence

ORD record
ord-8cb1cd91ee3c4c08af6c97bee098438c
Source dataset
uspto-grants-2015_01
Patent number
US08940733B2

Reaction notes

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