Sodium Iodide → (+/-)-Methyl(cis)-1-(4-isopropylbenzyl)-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate

HRID 1869743Notes

Reaction equation

[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:14][C@@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.[CH:21]([C:24]1[CH:31]=[CH:30][C:27]([CH2:28]Br)=[CH:26][CH:25]=1)([CH3:23])[CH3:22].[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[CH:21]([C:24]1[CH:31]=[CH:30][C:27]([CH2:28][N:10]2[CH2:11][CH2:12][C@H:13]([C:15]([O:17][CH3:18])=[O:16])[CH2:14][C@@H:9]2[C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:19])([F:1])[F:20])=[CH:8][CH:7]=2)=[CH:26][CH:25]=1)([CH3:23])[CH3:22]

Participants

Conditions

Temperature: 150 °C

Procedure

Methyl(cis)-2-[4-(trifluoromethyl)phenyl]piperidine-4-carboxylate (0.22 g), 4-isopropylbenzyl bromide (240 mg), NaI (15 mg), K2CO3 (287 mg) in DMF (2 ml) were placed in a microwave tube and the contents were heated in the microwave oven for 20 min at 150° C. The cooled mixture was dispersed between H2O and EtOAc and the organic extracts were washed with brine, dried (MgSO4) and evaporated. The crude oil was purified by chromatography on silica using 5-8% EtOAc in hexane to yield a colourless oil (260 mg, 81%) which crystallized on standing. 1H NMR (400 MHz, CDCl3) δ: 1.23 (6H, d, J 6.9), 1.71-1.81 (2H, m), 1.92 (1H, d, J 12.9), 1.97-2.04 (2H, m), 2.44-2.50 (1H, m), 2.82-2.90 (2H, m), 3.08-3.10 (1H, m), 3.25 (1H, dd, J 2.8, 11.3), 3.66 (4H, t, J 9.1), 7.14 (4H, q, J 6.3), 7.58 (4H, s); M/Z (ES+) 420 (MH+).

Workup

washthe organic extracts were washed with brine
dry with materialdried (MgSO4)
customevaporated
customThe crude oil was purified by chromatography on silica using 5-8% EtOAc in hexane

Sources & evidence

ORD record: ord-152469e75d9748a68f194f2fe7ef0b05
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07638629B2

Reaction notes

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