Lithium triethylborohydride → HCID 131736455, compound

HRID 1057072Notes

Reaction equation

HRID 1057072 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH2:11][C@H:12]4[C:18](=O)[N:17](COCC[Si](C)(C)C)[C:16]5[CH:28]=[C:29]([O:34][CH2:35][CH2:36][CH2:37][O:38][C:39]6[C:40]([O:84][CH3:85])=[CH:41][C:42]7[C:48](=[O:49])[N:47]8[CH:50]=[C:51](/[CH:53]=[CH:54]/[CH2:55][NH:56][C:57](=[O:73])[O:58][CH2:59][CH:60]9[C:72]%10[CH:71]=[CH:70][CH:69]=[CH:68][C:67]=%10[C:66]%10[C:61]9=[CH:62][CH:63]=[CH:64][CH:65]=%10)[CH2:52][C@H:46]8[C:45](=O)[N:44](COCC[Si](C)(C)C)[C:43]=7[CH:83]=6)[C:30]([O:32][CH3:33])=[CH:31][C:15]=5[C:14](=[O:86])[N:13]4[CH:87]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.[Li+].[B-](CC)(CC)CC>C1COCC1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH2:11][C@H:12]4[CH:18]=[N:17][C:16]5[CH:28]=[C:29]([O:34][CH2:35][CH2:36][CH2:37][O:38][C:39]6[C:40]([O:84][CH3:85])=[CH:41][C:42]7[C:48](=[O:49])[N:47]8[CH:50]=[C:51](/[CH:53]=[CH:54]/[CH2:55][NH:56][C:57](=[O:73])[O:58][CH2:59][CH:60]9[C:61]%10[CH:62]=[CH:63][CH:64]=[CH:65][C:66]=%10[C:67]%10[C:72]9=[CH:71][CH:70]=[CH:69][CH:68]=%10)[CH2:52][C@H:46]8[CH:45]=[N:44][C:43]=7[CH:83]=6)[C:30]([O:32][CH3:33])=[CH:31][C:15]=5[C:14](=[O:86])[N:13]4[CH:87]=3)=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

4

Reactant 2

HCID 23712863Lithium triethylborohydrideHCID 131736456HCID 131736456, compound

Product 1

HCID 131736455HCID 131736455, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

SEM dilactam 14d (0.223 g, 0.183 mmol, 1.0 eq.) was solubilised in THF (10 mL) and cooled to −78° C. under a nitrogen atmosphere. Super hydride solution (0.373 mL, 0.373 mmol, 2.04 eq.). was added dropwise over 5 minutes. After 20 minutes an aliquot was washed with water for LCMS and TLC analysis and after 30 minutes water (30 mL) was added and the cold bath removed. The organic layer was extracted with EtOAc (2×30 mL) and the combined organic extracts washed with brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was dissolved in MeOH (12 mL), DCM (6 mL) and water (2 mL) and enough silica gel to form a thick stirring suspension which was left for 5 days. The suspension was filtered and washed with DCM/MeOH 9:1 (˜200 mL) until complete elution of product. The organic layer was washed with brine (2×70 mL), dried over MgSO4, filtered and concentrated under reduced pressure and the residue was purified by flash chromatography (silica gel, 100/0 to 90/10 v/v CHCl3/MeOH) to afford the product as a yellow solid (0.133 g, 79%). LC/MS (2.916 min (ES+)), m/z: 926.33 [M+H]+.

Workup

  1. additionwas added dropwise over 5 minutes
  2. washAfter 20 minutes an aliquot was washed with water for LCMS and TLC analysis and after 30 minutes water (30 mL)
  3. additionwas added
  4. customthe cold bath removed
  5. extractionThe organic layer was extracted with EtOAc (2×30 mL)
  6. washthe combined organic extracts washed with brine (30 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe crude product was dissolved in MeOH (12 mL)
  11. customDCM (6 mL) and water (2 mL) and enough silica gel to form a thick stirring suspension which
  12. filtrationThe suspension was filtered
  13. washwashed with DCM/MeOH 9:1 (˜200 mL) until complete elution of product
  14. washThe organic layer was washed with brine (2×70 mL)
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure
  18. customthe residue was purified by flash chromatography (silica gel, 100/0 to 90/10 v/v CHCl3/MeOH)

Sources & evidence

ORD record
ord-b50599ccca124789ba52025020dbf37e
Source dataset
uspto-grants-2016_07
Patent number
US09399073B2

Reaction notes

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