Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate → HCID 57546007, compound

HRID 913977Notes

Reaction equation

HRID 913977 reaction equation
ClC(Cl)(Cl)C(=N)O[CH:5]([C:7]1[C:15]2[N:14]=[CH:13][N:12]([CH2:16][CH3:17])[C:11]=2[CH:10]=[C:9]([C:18]([F:21])([F:20])[F:19])[CH:8]=1)[CH3:6].[F:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2([CH2:45][OH:46])[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)=[CH:28][CH:27]=1.ClC(Cl)C.C1CCCCC1>>[CH2:16]([N:12]1[C:11]2[CH:10]=[C:9]([C:18]([F:21])([F:19])[F:20])[CH:8]=[C:7]([CH:5]([O:46][CH2:45][C:32]3([C:29]4[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=4)[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:42])([CH3:43])[CH3:44])=[O:39])[CH2:36][CH2:37]3)[CH3:6])[C:15]=2[N:14]=[CH:13]1)[CH3:17]

Participants

4

Reactant 3

HCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylateHCID 21916605HCID 21916605, compoundHCID 57546123HCID 57546123, compound

Product 1

HCID 57546007HCID 57546007, compound

Conditions

Temperature
0 °C

Procedure

(±)-(1-(1-Ethyl-6-(trifluoromethyl)-1H-benzo[d]imidazol-4-yl)ethyl 2,2,2-trichloroacetimidate (670 mg, 1.7 mmol) and tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (772 mg, 2.5 mmol) were combined in a dichloroethane/cyclohexane mixture (4:2, 6 mL) and cooled to 0° C. The reaction mixture was treated with tetrafluoroboric acid-diethyl ether complex (91 μL, 0.67 mmol), and subsequent processing including extractive work up and purification were carried out as described in example 8 to give 281 mg (30.7%) as white foam-like solid. 1H-NMR (500 MHz, CHLOROFORM-D) δ ppm 7.97 (s, 1 H), 7.54 (s, 1 H), 7.20-7.33 (m, 3 H), 7.00 (t, J=8.7 Hz, 2 H), 5.10 (q, J=6.6 Hz, 1 H), 4.17-4.30 (m, 2 H), 3.56-3.78 (m, 2 H), 3.24-3.40 (m, 2 H), 2.93-3.12 (m, 2 H), 2.02-2.21 (m, 2 H), 1.80-1.99 (m, 2 H), 1.56 (t, 3 H), 1.37-1.47 (m, 12 H). 550.40 (MH)+.

Workup

  1. additionThe reaction mixture was treated with tetrafluoroboric acid-diethyl ether complex (91 μL, 0.67 mmol), and subsequent processing
  2. custompurification
  3. customto give 281 mg (30.7%) as white foam-like solid

Sources & evidence

ORD record
ord-f4fb8081ece84abe8f449bcd00e599e7
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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