Cyclohexane → HCID 57546243, compound

HRID 913869Notes

Reaction equation

HRID 913869 reaction equation
ClC(Cl)(Cl)C(=N)O[CH:5]([C:7]1[C:15]2[C:11](=[CH:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:14]=2)[CH:10]=[C:9]([F:24])[CH:8]=1)[CH3:6].[F:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]2([CH2:48][OH:49])[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]2)=[CH:31][CH:30]=1.C1CCCCC1>ClCCl>[F:24][C:9]1[CH:8]=[C:7]([CH:5]([O:49][CH2:48][C:35]2([C:32]3[CH:31]=[CH:30][C:29]([F:28])=[CH:34][CH:33]=3)[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:45])([CH3:46])[CH3:47])=[O:42])[CH2:39][CH2:40]2)[CH3:6])[C:15]2[C:11](=[CH:12][N:13]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:22])([CH3:21])[CH3:23])[N:14]=2)[CH:10]=1

Participants

5

Reactant 3

HCID 8078CyclohexaneHCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 57546044HCID 57546044, compound

Product 1

HCID 57546243HCID 57546243, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-1-(5-fluoro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-7-yl)ethyl 2,2,2-trichloroacetimidate (1.121 g, 2.465 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (0.839 g, 2.71 mmol) in dichloromethane (6 mL) at 0° C. was added cyclohexane (5.61 mL) and tetrafluoroboric acid diethyl ether complex (0.017 mL, 0.123 mmol). The reaction was stirred at 0° C. for 10 min. The reaction was treated with an additional portion of tetrafluoroboric acid diethyl ether complex (9 μL, 0.065 mmol) and stirred at 0° C. for 30 min. The reaction was quenched by addition of saturated sodium bicarbonate, diluted with diethyl ether, and poured into water. The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (15%→22% EtOAc/Hex) gave 922 mg (62.2%) as an amorphous foam solid. 1H-NMR (CDCl3, 300 MHz) δ 7.98 (s, 1H), 7.26-7.32 (m, 2H), 6.97-7.08 (m, 3H), 6.64-6.68(m, 1H), 5.62 (s, 2H), 4.92 (q, J=6.0 Hz, 1H), 3.65-3.75 (m, 2H), 3.58 (m, 2H), 3.35 (m, 2H), 2.9-3.1 (m, 2H), 1.8-2.2 (m, 4H), 1.39-1.42(m, 12H), 0.88(m, 2H), −0.07 (s, 9H); Mass spec.: 602.54 (MH)+.

Workup

  1. additionThe reaction was treated with an additional portion of tetrafluoroboric acid diethyl ether complex (9 μL, 0.065 mmol)
  2. stirringstirred at 0° C. for 30 min
  3. customThe reaction was quenched by addition of saturated sodium bicarbonate
  4. additiondiluted with diethyl ether
  5. additionpoured into water
  6. washThe ethereal was washed with water (2×)
  7. dry with materialbrine, dried over magnesium sulfate
  8. concentrationconcentrated
  9. customColumn chromatography (15%→22% EtOAc/Hex) gave 922 mg (62.2%) as an amorphous foam solid

Sources & evidence

ORD record
ord-8d641e42605b43bdb6316bf4f373a5a5
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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