Lithium triethylborohydride → HCID 68231371, compound

HRID 1482763Notes

Reaction equation

HRID 1482763 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][C@H:10]3[C:16](=O)[N:15](COCC[Si](C)(C)C)[C:14]4[CH:26]=[C:27]([O:32][CH2:33][CH2:34][CH2:35][O:36][C:37]5[C:38]([O:64][CH3:65])=[CH:39][C:40]6[C:46](=[O:47])[N:45]7[CH:48]=[C:49]([CH:51]8[CH2:53][CH2:52]8)[CH2:50][C@H:44]7[C:43](=O)[N:42](COCC[Si](C)(C)C)[C:41]=6[CH:63]=5)[C:28]([O:30][CH3:31])=[CH:29][C:13]=4[C:12](=[O:66])[N:11]3[CH:67]=2)=[CH:4][CH:3]=1.[Li+].[B-](CC)(CC)CC>C1COCC1>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH2:9][C@H:10]3[CH:16]=[N:15][C:14]4[CH:26]=[C:27]([O:32][CH2:33][CH2:34][CH2:35][O:36][C:37]5[C:38]([O:64][CH3:65])=[CH:39][C:40]6[C:46](=[O:47])[N:45]7[CH:48]=[C:49]([CH:51]8[CH2:53][CH2:52]8)[CH2:50][C@H:44]7[CH:43]=[N:42][C:41]=6[CH:63]=5)[C:28]([O:30][CH3:31])=[CH:29][C:13]=4[C:12](=[O:66])[N:11]3[CH:67]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 23712863Lithium triethylborohydrideHCID 86717253HCID 86717253, compound

Product 1

HCID 68231371HCID 68231371, compoundYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

SEM dilactam 14 (0.66 g, 0.69 mmol) was dissolved in THF (23 mL) and cooled to −78° C. under an argon atmosphere. Super-Hydride® solution (1.7 mL, 1 M in THF) was added drop wise over 5 minutes while monitoring the temperature. After 20 minutes a small sample was taken and washed with water for LC/MS analysis. Water (50 mL) was added and the cold bath was removed. The organic layer was extracted and washed with brine (60 mL). The combined aqueous layers were washed with CH2Cl2/MeOH (90/10 v/v) (2×50 mL). The combined organic layers were dried with MgSO4, filtered and the solvent removed in vacuo. The crude product was dissolved in MeOH (48 mL), CH2Cl2 (18 mL) and water (6 mL) and sufficient silica gel was added to afford a thick suspension. After 5 days stirring, the suspension was filtered through a sintered funnel and washed with CH2Cl2/MeOH (9:1) (˜200 mL) until product ceased to be eluted. The organic layer was washed with brine (2×70 mL), dried with MgSO4, filtered and the solvent removed in vacuo. Purification by silica gel column chromatography (100% CHCl3 to 96/4 v/v CHCl3/MeOH) afforded the product 15 as a yellow solid (302 mg, 66%). Method 1, LC/MS (2.42 min (ES+) m/z (relative intensity) 660.74 ([M+H]+, 30). 1H NMR (400 MHz, CDCl3) d 7.86 (d, 1H, J=3.6 Hz), 7.78 (d, 1H, J=3.6 Hz), 7.58-7.44 (m, 3H), 7.34-7.20 (m, 3H), 6.88-6.66 (m, 4H), 4.35-4.15 (m, 6H), 3.95-3.75 (m, 7H), 3.39-3.22 (m, 1H), 3.14-3.04 (m, 1H), 2.93-2.85 (m, 1H), 2.46-2.36 (m, 2H), 1.49-1.41 (m, 1H), 0.80-0.72 (m, 2H), 0.58-0.51 (app. s, 2H) ppm.

Workup

  1. washwashed with water for LC/MS analysis
  2. additionWater (50 mL) was added
  3. customthe cold bath was removed
  4. extractionThe organic layer was extracted
  5. washwashed with brine (60 mL)
  6. washThe combined aqueous layers were washed with CH2Cl2/MeOH (90/10 v/v) (2×50 mL)
  7. dry with materialThe combined organic layers were dried with MgSO4
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. dissolutionThe crude product was dissolved in MeOH (48 mL)
  11. additionCH2Cl2 (18 mL) and water (6 mL) and sufficient silica gel was added
  12. customto afford a thick suspension
  13. filtrationthe suspension was filtered through a sintered funnel
  14. washwashed with CH2Cl2/MeOH (9:1) (˜200 mL) until product
  15. washto be eluted
  16. washThe organic layer was washed with brine (2×70 mL)
  17. dry with materialdried with MgSO4
  18. filtrationfiltered
  19. customthe solvent removed in vacuo
  20. customPurification by silica gel column chromatography (100% CHCl3 to 96/4 v/v CHCl3/MeOH)

Sources & evidence

ORD record
ord-bbf3e3f2ddcf4db2a382b3e1caf2480d
Source dataset
uspto-grants-2016_08
Patent number
US09415117B2

Reaction notes

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