Potassium Hydroxide → HCID 57545980, compound

HRID 913848Notes

Reaction equation

HRID 913848 reaction equation
Br[C:2]1[CH:10]=[C:9]([CH:11]([O:13][CH2:14][C:15]2([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH3:12])[C:8]2[C:4](=[CH:5][N:6]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:7]=2)[CH:3]=1.[CH:43]1(B(O)O)[CH2:45][CH2:44]1.[OH-].[K+]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:43]1([C:2]2[CH:10]=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20]3)[CH3:12])[C:8]3[C:4](=[CH:5][N:6]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:41])([CH3:40])[CH3:42])[N:7]=3)[CH:3]=2)[CH2:45][CH2:44]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 2760897Cyclopropylboronic acidHCID 57546111(+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 57545980HCID 57545980, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

(±)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (75 mg, 0. 113 mmol), cyclopropyl boronic acid (20 mg, 0.34 mmol), and tetrakis(triphenylphosphine) palladium(0) (13. 1 mg, 0.011 mmol) were combined in dry tetrahydrofuran (2 mL) followed by addition of 0.58 mL of a 1 N aqueous potassium hydroxide solution in a microwave tube and sealed. After flushing the mixture with nitrogen, the mixture was heated at 100° C. for 1 h via microwave. After cooling to room temperature, the reaction mixture was concentrated, dissolved in ethyl acetate and washed with water and brine, concentrated and purified by flash chromatography on silica gel (20% EtOAc/Hex) to afford 70.5 mg (100%) as an oil. LC/MS (HPLC method 2): tR=3.738 min, 624.24(MH)+.

Workup

  1. customsealed
  2. customAfter flushing the mixture with nitrogen
  3. temperatureAfter cooling to room temperature
  4. concentrationthe reaction mixture was concentrated
  5. dissolutiondissolved in ethyl acetate
  6. washwashed with water and brine
  7. concentrationconcentrated
  8. custompurified by flash chromatography on silica gel (20% EtOAc/Hex)
  9. customto afford 70.5 mg (100%) as an oil

Sources & evidence

ORD record
ord-7cc0224b779c48d9895fff922e7f3b09
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

Loading…