Lithium triethylborohydride → HCID 57546060, compound

HRID 913958Notes

Reaction equation

HRID 913958 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:19][CH2:20][C:21]2([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH2:12][CH2:13]OS(C)(=O)=O)[C:8]2[C:4](=[CH:5][N:6]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[N:7]=2)[CH:3]=1.[Li+].[B-](CC)(CC)CC>C1COCC1.CCOCC.O>[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:19][CH2:20][C:21]2([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH2:12][CH3:13])[C:8]2[C:4](=[CH:5][N:6]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:46])[CH3:47])[N:7]=2)[CH:3]=1

Participants

6

Reactant 2

HCID 23712863Lithium triethylborohydride3×HCID 57546165HCID 57546165, compound

Product 1

HCID 57546060HCID 57546060, compoundYield 61.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-3-(methylsulfonyloxy)propoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (28.5 mg, 0.039 mmol) in THF (1 ml) at 0° C. was added Superhydride (0.059 ml, 0.059 mmol). It was stirred at R.T. over three hours, LC/MS showed no reaction. Another 1.5 eq of super hydride was added and it was stirred at R.T. overnight. LC/MS showed partial convertion to product, another 1.5eq of superhydride was added and it was stirred at R.T. overweekend. LC/MS showed the reaction was complete. The reaction was cooled to 0° C. and diluted with ether, water was added and layer separated, the organics were washed with brine and dried over magnesium sulfate, filtered and concentrated. It was purified by Biotage LC eluting with 25% EtOAc/Hex to afford title compound (15 mg, 0.024 mmol, 60.5% yield) as clear oil. 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H), 7.48 (d, J=1.6 Hz, 1H), 7.48 (d, J=1.6 Hz, 1H), 7.31 (m, 2H), 7.03 (t, J=8.9 Hz, 2H), 6.68 (s, 1H), 5.66 (AB, Δν=17.4 Hz, J=10.7 Hz, 2H), 4.77 (m, 1H), 3.72 (m, 2H), 3.59 (t, J=8.2 Hz, 2H), 3.34 (AB, Δν=23.5 Hz, J=8.8 Hz, 2H), 3.09 (m, 2H), 2.40 (m, 1H), 2.12 (m, 1H), 1.96 (m, 1H), 1.84 (m, 2H), 1.70 (m, 1H), 1.44 (s, 9H), 0.91 (m, 2H), 0.84 (t, J=7.3 Hz, 3H), −0.06 (s, 9H). LC/MS (HPLC method 4): tR=4.99 min, 632.2(MH)+.

Workup

  1. customno reaction
  2. stirringit was stirred at R.T. overnight
  3. stirringit was stirred at R.T. overweekend
  4. temperatureThe reaction was cooled to 0° C.
  5. additionwas added
  6. customlayer separated
  7. washthe organics were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customIt was purified by Biotage LC
  12. washeluting with 25% EtOAc/Hex

Sources & evidence

ORD record
ord-94c22c74799a4aedaffe13293a999582
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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