Tetrabutylammonium Fluoride → tert-Butyl 4-((1-(5-chloro-1H-indazol-7-yl)-2-fluoroethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

HRID 913933Notes

Reaction equation

HRID 913933 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH2:12][F:13])[C:8]2[C:4](=[CH:5][N:6](COCC[Si](C)(C)C)[N:7]=2)[CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:14][CH2:15][C:16]3([C:29]4[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=4)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[CH2:12][F:13])[CH:10]=1)[NH:7][N:6]=[CH:5]2

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 57545990HCID 57545990, compound

Product 1

HCID 57546100tert-Butyl 4-((1-(5-chloro-1H-indazol-7-yl)-2-fluoroethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

tert-Butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-fluoroethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (40 mg, 0.063 mmol) was dissolved in tetrabutylammonium fluoride (1M in tetrahydrofuran, 0.8 mL, 0.8 mmol). The flask was sealed and placed in a 55° C. bath. After 1.5 h, the reaction was cooled to room temperature, diluted with diethyl ether, washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (50%→60% ethyl acetate/n-hexane) gave 29 mg (91%) as a colorless oil. 1H-NMR (CDCl3, 500 MHz) δ 9.82 (bs, 1H), 7.91 (s, 1H), 7.63 (d, J=1.8 Hz, 1H), 7.27 (dd, J=89., 5.5 Hz, 2H), 7.07 (dd, J=8.9, 8.5 Hz, 2H), 7.03 (d, J=1.5 Hz, 1H), 4.61 (ddd, J=18.0, 5.2, 4.6 Hz, 1H), 4.53 (d, J=4.6 Hz, 1H), 4.44 (d, J=4.9 Hz, 1H), 3.74 (m, 2H), 3.49 (d, J=9.2 Hz, 1H), 3.39 (d, J=9.2 Hz, 1H), 3.06 (m, 1H), 2.97 (m, 1H), 2.30 (m, 1H), 2.06 (m, 1H), 1.87 (m, 1H), 1.75 (m, 1H), 1.43 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.7 (d, J=247 Hz), 155.0, 137.7, 136.4, 133.8, 128.8 (d, J=7.7 Hz), 126.2, 125.6, 124.9, 121.0, 120.9, 120.2, 115.8 (d, J=21 Hz), 85.8, 84.4, 81.3, 81.1, 79.8, 79.7, 41.4, 40.3, 39.6, 32.4, 32.1, 28.5. Mass spec.: 506.23 (MH)+.

Workup

  1. customThe flask was sealed
  2. customplaced in a 55° C.
  3. washwashed with water
  4. dry with materialbrine, dried over magnesium sulfate
  5. concentrationconcentrated
  6. customColumn chromatography (50%→60% ethyl acetate/n-hexane) gave 29 mg (91%) as a colorless oil

Sources & evidence

ORD record
ord-198298d03ec8423cbcba2d146abee063
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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