N-Methyl dicyclohexylamine → (+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913846Notes

Reaction equation

HRID 913846 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[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)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2.CN(C1CCCCC1)C1CCCCC1.Cl[CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55]>O1CCCC1>[Br:1][C:2]1[CH:10]=[C:9]([CH:11]([O:13][CH2:14][C:15]2([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH3:12])[C:8]2[C:4](=[CH:5][N:6]([CH2:50][O:51][CH2:52][CH2:53][Si:54]([CH3:57])([CH3:56])[CH3:55])[N:7]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 24210N-Methyl dicyclohexylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 57545919(+/-)-tert-butyl 4-((1-(5-bromo-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (±)-tert-butyl 4-((1-(5-bromo-1H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (340 mg, 0.639 mmol) and N-methyldicyclohexylamine (0.205 mL, 0.958 mmol) in tetrahydrofuran (2 mL) at 0° C. was added (2-(chloromethoxy)ethyl)trimethylsilane (0. 159 mL, 0.894 mmol). The ice bath was removed and the reaction stirred at room temperature overnight. The reaction was poured into diethyl ether, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (12%→25% EtOAc/Hex) gave 383 mg (91%) as a foam. 1H-NMR (CDCl3, 500 MHz) δ 7.99 (s, 1H), 7.66 (s, 1H), 7.30 (m, 2H), 7.02 (m, 2H), 6.89 (s, 1H), 5.64 (qAB, JAB=10.7, 2H), 4.92 (q, J=6.4, 1H), 3.71 (m, 2H), 3.59 (m, 2H), 3.35 (qAB, JAB=9.2, 2H), 3.05 (m, 2H), 2.18 (m, 1H), 2.06 (m, 1H), 1.93 (m, 1H), 1.86 (m, 1H), 1.42 (m, 12H), 0.90 (m, 2H), −0.07 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 162.4, 160.5, 155.1, 145.6, 138.8, 135.9, 128.9 (d, J=7.7), 124.9, 123.6, 122.2, 121.1, 116.2, 115.3, 115.2, 81.9, 79.4, 77.9, 73.9, 67.6, 41.3, 40.3 (br), 32.3, 31.9, 28.6, 22.9, 17.9, −1.3.

Workup

  1. customThe ice bath was removed
  2. additionThe reaction was poured into diethyl ether
  3. washwashed with water (2×)
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated
  6. customColumn chromatography (12%→25% EtOAc/Hex) gave 383 mg (91%) as a foam

Sources & evidence

ORD record
ord-13db0669d59b4980b6151dd005d1625c
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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