Cyclohexane → HCID 57546173, compound

HRID 913894Notes

Reaction equation

HRID 913894 reaction equation
ClC(Cl)(Cl)C(=N)[O:4][CH:5]([C:7]1[CH:8]=[C:9]([C:24]([F:27])([F:26])[F:25])[CH:10]=[C:11]2[C:15]=1[N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH:13]=[CH:12]2)[CH3:6].[F:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2([CH2:51]O)[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]2)=[CH:34][CH:33]=1.C1CCCCC1>>[F:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2([CH2:51][O:4][CH:5]([C:7]3[CH:8]=[C:9]([C:24]([F:26])([F:27])[F:25])[CH:10]=[C:11]4[C:15]=3[N:14]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:21])[CH3:22])[CH:13]=[CH:12]4)[CH3:6])[CH2:39][CH2:40][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:42][CH2:43]2)=[CH:34][CH:33]=1

Participants

4

Reactant 3

HCID 8078CyclohexaneHCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 57546252HCID 57546252, compound

Product 1

HCID 57546173HCID 57546173, compoundYield 52.5%

Conditions

Temperature
0 °C

Procedure

To a solution of (±)-1-(5-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indol-7-yl)ethyl 2,2,2-trichloroacetimidate (361 mg, 0.716 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (244 mg, 0.788 mmol) at 0° C. was added cyclohexane (2 ml, 18.49 mmol) and fluoroboric acid diethyl ether complex (0.019 ml, 0.143 mmol). The reaction was stirred at 0° C. for 45 min and was judged complete by TLC. The reaction was quenched with aqueous sodium bicarbonate (5 mL) and extracted with ethyl acetate (3×5 mL). The combined organic layers were dried with magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with a gradient of ethyl acetate/hexanes from 12% to 100%. The product (245 mg, 0.376 mmol, 52.5% yield) was isolated as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.77 (m, 1H), 7.34 (s, 1H), 7.18 (m, 2H), 7.08 (d, J=3.7 Hz, 1H), 6.94 (m, 2H), 6.54 (m, 1H), 5.29 (m, 2H), 5.18 (m, 1H), 3.65 (m, 2H), 3.33 (m, 2H), 3.24 (m, 1H), 3.14 (m, 1H), 3.00 (m, 2H), 2.03 (m, 2H), 1.86 (m, 2H), 1.44 (d, J=6.4 Hz, 3H), 1.419 (s, 9H), 0.74 (m, 2H), −0.09 (s, 9H); LC/MS (HPLC method 4): tR=4.871 min, 651.28(MH)+.

Workup

  1. customThe reaction was quenched with aqueous sodium bicarbonate (5 mL)
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. dry with materialThe combined organic layers were dried with magnesium sulfate
  4. customevaporated
  5. customThe residue was purified by chromatography on silica gel with a gradient of ethyl acetate/hexanes from 12% to 100%

Sources & evidence

ORD record
ord-248623caa7454d3999356ffeed2ba216
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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