Cyclohexane → HCID 57546247, compound

HRID 913893Notes

Reaction equation

HRID 913893 reaction equation
ClC(Cl)(Cl)C(=N)O[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].[OH:31][CH2:32][C:33]1([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]1.C1CCCCC1>ClCCl>[C:46]1([C:33]2([CH2:32][O:31][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]([CH3:21])([CH3:22])[CH3:23])[CH:13]=[CH:12]4)[CH3:6])[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:44])([CH3:45])[CH3:43])=[O:40])[CH2:35][CH2:34]2)[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

5

Reactant 3

HCID 8078CyclohexaneHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 57546252HCID 57546252, compound

Product 1

HCID 57546247HCID 57546247, compoundYield 47.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (290 mg, 0.576 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (184 mg, 0.633 mmol) in dichloromethane (2 mL) at 0° C. was added cyclohexane (2 ml) and fluoroboric acid diethyl ether complex (0.016 ml, 0.115 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 (173 mg, 0.273 mmol, 47.5% yield) was isolated as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.77 (m, 1H), 7.39 (m, 1H), 7.14-7.29 (m, 5H), 7.07 (m, 1H), 6.54 (m, 1H), 5.15 (m, 1H), 3.32 (m, 2H), 3.21 (m, 2H), 3.00 m, 2H), 2.11 (m, 2H), 1.88 (m, 2H), 1.45 (d, J=6.4 Hz, 3H), 1.42 (s, 9H), 0.75 (m, 2H), −0.09 (s, 9H); LC/MS (HPLC method 4): tR=4.36 min, 655.20(MNa)+.

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-2256ce354d5d48f7b8f707d22c31cdd6
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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