Perfluoro-1-butanesulfonyl fluoride → HCID 57545990, compound

HRID 913932Notes

Reaction equation

HRID 913932 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]O)[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:7]=2)[CH:3]=1.C(N(C(C)C)CC)(C)C.F.F.F.C(N(C(C)C)CC)(C)C.[F:65]C(F)(S(F)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F.C(=O)(O)[O-].[Na+]>C(#N)C.C(OCC)C>[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]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:18][CH2:17]2)[CH2:12][F:65])[C:8]2[C:4](=[CH:5][N:6]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:42])([CH3:43])[CH3:41])[N:7]=2)[CH:3]=1

Participants

8

Reactant 5

HCID 67814Perfluoro-1-butanesulfonyl fluorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 45108321N-Ethyl-N-(propan-2-yl)propan-2-amine--hydrogen fluoride (1/3)HCID 57545941HCID 57545941, compound

Product 1

HCID 57545990HCID 57545990, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of tert-butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-hydroxyethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (50 mg, 0.079 mmol) in acetonitrile (0.1 mL) at room temperature was added diisopropylethylamine (0.062 mL, 0.355 mmol), diisopropylethylamine trihydrofluoride (22.4 mg, 0.118 mmol), and perfluoro-1-butanesulfonyl fluoride (0.028 mL, 0.16 mmol). The reaction was stirred at room temperature overnight. The reaction was poured into saturated sodium bicarbonate, and diluted with diethyl ether. The ethereal was washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (15%→20% ethyl acetate/n-hexane) gave 40 mg (80%) as a colorless film. 1H-NMR (CDCl3, 500 MHz) δ 8.01 (s, 1H), 7.54 (d, J=1.8 Hz, 1H), 7.33 (dd, J=9.2, 5.5 Hz, 2H), 7.03 (dd, J=8.9, 8.5 Hz, 2H), 6.73 (bs, 1H), 5.66 (d, J=10.7 Hz, 1H), 5.63 (d, J=10.7 Hz, 1H), 5.16 (m, 1H), 4.62 (ddd, J=46.7, 9.5, 2.4 Hz, 1H), 4.42 (ddd, J=48.2, 9.8, 7.3 Hz, 1H), 3.75 (bs, 2H), 3.60 (m, 2H), 3.52 (d, J=9.2 Hz, 1H), 3.45 (d, J=9.2 Hz, 1H), 3.10 (bs, 1H), 3.03 (m, 1H), 2.27 (m, 1H), 2.07 (m, 1H), 1.99 (m, 1H), 1.87 (m, 1H), 1.44 (s, 9H), 0.92 (m, 2H), −0.05 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 161.5 (d, J=246 Hz), 155.1, 145.4, 138.5, 128.9 (d, J=7.7 Hz), 128.2, 128.11, 128.07, 124.9, 122.7, 122.6, 118.9, 115.3 (d, J=21 Hz), 85.9, 84.4, 81.9, 79.5, 78.8, 77.3, 77.1, 67.8, 41.5, 40.5, 39.7, 32.2, 31.8, 28.6, 17.9, −1.4. Mass spec.: 636.43 (MH)+.

Workup

  1. washThe ethereal was washed with water
  2. dry with materialbrine, dried over magnesium sulfate
  3. concentrationconcentrated
  4. customColumn chromatography (15%→20% ethyl acetate/n-hexane) gave 40 mg (80%) as a colorless film

Sources & evidence

ORD record
ord-45ec5189f3a34364b7da5ce72d3853d6
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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