Sodium Carbonate → (+/-)-tert-Butyl 4-(4-fluorophenyl)-4-((1-(5-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)piperidine-1-carboxylate

HRID 913852Notes

Reaction equation

HRID 913852 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.[CH3:43]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>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>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:15]2([CH2:14][O:13][CH:11]([C:9]3[C:8]4[C:4](=[CH:5][N:6]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[N:7]=4)[CH:3]=[C:2]([CH3:43])[CH:10]=3)[CH3:12])[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)=[CH:29][CH:30]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 574072TrimethylboroxineHCID 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 57546097(+/-)-tert-Butyl 4-(4-fluorophenyl)-4-((1-(5-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °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 (150 mg, 0.226 mmol), trimethylboroxine (0.063 mL, 0.453 mmol), and tetrakis(triphenylphosphine) palladium(0) (13.1 mg, 0.011 mmol) were combined in dry tetrahydrofuran (1. 1 mL) and 4 M sodium carbonate (0.17 mL ) in a microwave tube and sealed. After flushing the mixture with nitrogen, the mixture was heated at 110° C. for 2 h via microwave. After cooling to room temperature, the reaction mixture was concentrated, dissolved in diethyl ether and washed with water and brine, concentrated and purified by flash chromatography on silica gel (20-25% EtOAc/Hex) to afford 49 mg (36.2%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 7.93 (s, 1H), 7.32 (m, 2H), 7.24 (s, 1H), 7.02 (m, 2H), 6.66 (s, 1H), 5.65 (s, 2H), 4.96 (d, J=5 Hz, 1H), 3.33-3.75 (m, 6H), 3.0-3.15 (m, 2H), 2.29 (s, 3H), 1.85-2.2 (m, 4H), 1.43 (m, 12H), 0.89 (m, 2H), −0.06 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 161.4 (d, J=974 Hz), 155.1, 146.2, 139.2, 133.3, 131.7, 129.1, 129.0, 124.0, 122.8, 121.8, 117.1, 115.1, 114.9, 81.7, 79.4, 77.6, 74.1, 67.3, 65.9, 41.3, 28.6, 23.1, 21.9, 17.9, 15.4, −1.4; Mass spec.: 598.45(MH)+.

Workup

  1. customAfter flushing the mixture with nitrogen
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction mixture was concentrated
  4. dissolutiondissolved in diethyl ether
  5. washwashed with water and brine
  6. concentrationconcentrated
  7. custompurified by flash chromatography on silica gel (20-25% EtOAc/Hex)
  8. customto afford 49 mg (36.2%) as an oil

Sources & evidence

ORD record
ord-2e72797a3e114d2ab744f9e3ca3b0c0a
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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