Sodium Carbonate → tert-Butyl 4-(((5-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

HRID 913803Notes

Reaction equation

HRID 913803 reaction equation
Br[C:2]1[CH:10]=[C:9]([CH2:11][O:12][CH2:13][C:14]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[C:8]2[C:4](=[CH:5][N:6]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:7]=2)[CH:3]=1.[CH3:41]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[Na+].[Na+]>[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.O1CCCC1>[CH3:41][C:2]1[CH:10]=[C:9]([CH2:11][O:12][CH2:13][C:14]2([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:16][CH2:15]2)[C:8]2[C:4](=[CH:5][N:6]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[N:7]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 574072TrimethylboroxineHCID 57546228tert-butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 57546241tert-Butyl 4-(((5-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

A microwave tube was charged with tert-butyl 4-(((5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (200 mg, 0.3 17 mmol), trimethylboroxine (0.089 mL, 0.634 mmol), tetrahydrofuran (1.5 mL), sodium carbonate (4 M in water, 0.24 mL, 0.95 mmol), and tetrakis(triphenylphosphine)-palladium(0) (18.3 mg, 0.016 mmol). The tube was flushed with nitrogen, sealed, and heated at 110° C. for 2 h via microwave. The reaction was cooled, poured into diethyl ether, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25% EtOAc/Hex) gave 86 mg (50%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ 7.94 (s, 1H), 7.20-7.45 (m, 6H), 6.86 (s, 1H), 5.65 (s, 2H), 4.84 (s, 2H), 3.74 (bs, 2H), 3.58 (t, J=7.9 Hz, 2H), 3.54 (s, 2H), 3.07 (m, 2H), 2.33 (s, 3H), 2.20 (m, 2H), 1.97 (m, 2H), 1.44 (s, 9H), 0.91 (t, J=7.6 Hz, 2H), −0.04 (s, 9H); 13C-NMR (CDCl3, 126 MHz) δ 155.1, 146.1, 143.2, 131.6, 128.5, 127.9, 127.4, 126.4, 126.0, 122.6, 121.9, 117.3, 81.7, 79.6, 79.3, 69.0, 67.3, 41.9, 40.3 (br), 32.0, 28.6, 22.0, 17.9, −1.3. Mass spec.: 566.35 (MH)+.

Workup

  1. customThe tube was flushed with nitrogen
  2. customsealed
  3. temperatureThe reaction was cooled
  4. additionpoured into diethyl ether
  5. washwashed with water (2×)
  6. dry with materialbrine, dried over magnesium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography (25% EtOAc/Hex) gave 86 mg (50%) as a colorless oil

Sources & evidence

ORD record
ord-32fbcd892f6443b3943bd240ff2a73b6
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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