Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate → HCID 57546158, compound

HRID 913886Notes

Reaction equation

HRID 913886 reaction equation
ClC(Cl)(Cl)C(=N)O[CH:5]([C:7]1[C:15]2[C:11](=[CH:12][N:13]([CH:16]3[CH2:18][CH2:17]3)[N:14]=2)[CH:10]=[C:9]([Cl:19])[CH:8]=1)[CH3:6].[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2([CH2:43][OH:44])[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]2)=[CH:26][CH:25]=1>ClCCl.C1CCCCC1>[Cl:19][C:9]1[CH:8]=[C:7]([CH:5]([O:44][CH2:43][C:30]2([C:27]3[CH:26]=[CH:25][C:24]([F:23])=[CH:29][CH:28]=3)[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])[CH2:34][CH2:35]2)[CH3:6])[C:15]2[C:11](=[CH:12][N:13]([CH:16]3[CH2:18][CH2:17]3)[N:14]=2)[CH:10]=1

Participants

4

Reactant 2

HCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 57546048HCID 57546048, compound

Product 1

HCID 57546158HCID 57546158, compound

Reagents, catalysts & solvents 1

HCID 21916607Dichloromethane cyclohexaneSolvent

Conditions

Temperature
0 °C

Procedure

(±)-1-(5-Chloro-2-cyclopropyl-2H-indazol-7-yl)ethyl 2,2,2-trichloroacetimidate (365 mg, 0.96 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (366 mg, 1.05 mmol) were combined in a dichloromethane/cyclohexane mixture (1:1, 10 mL) and cooled to 0° C. The reaction was treated with tetrafluoroboric acid-diethyl ether complex (26 μL, 0.19 mmol), stirred at 0° C. for 1 h, quenched by addition of saturated sodium bicarbonate and diluted with diethyl ether. The layers were separated. The ethereal was washed with water (2×), brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (18% ethyl acetate/hexanes) gave 0.32 g (62%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 7.86 (s, 1H), 7.40 (m, 1H), 7.28-7.31 (m, 2H), 6.99-7.03 (m, 2H), 6.75 (m, 1H), 4.90 (q, J=6.4 Hz, 1H), 3.86-3.90(m, 2H), 3.32-3.36 (m, 2H), 3.00-3.09 (m, 2H), 2.04-2.17 (m, 2H), 1.84-1.95 (m, 2H), 1.43 (s, 9H), 1.41 (d, J=6.4 Hz, 3H), 1.26-1.30 (m, 2H), 1.12-1.16 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 163.7, 161.4 (d, J=244.7 Hz), 152.2, 145.3, 138.9, 135.1, 128.9, 127.7, 122.3, 117.2, 115.2, 115.1, 79.5, 77.8, 73.9, 60.5, 41.3, 34.7, 28.6, 22.7, 14.3, 7.4. Mass spec.: 528.62 (MH)+.

Workup

  1. additionThe reaction was treated with tetrafluoroboric acid-diethyl ether complex (26 μL, 0.19 mmol)
  2. customquenched by addition of saturated sodium bicarbonate
  3. additiondiluted with diethyl ether
  4. customThe layers were separated
  5. washThe ethereal was washed with water (2×), brine (2×)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography on silica gel (18% ethyl acetate/hexanes) gave 0.32 g (62%) as an oil

Sources & evidence

ORD record
ord-a4f571e422ad47e882db99da3d47fbcb
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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