Monobenzone → tert-Butyl 4-[2-[4-(Benzyloxy)phenoxy]ethyl]piperidine-1-carboxylate

HRID 2095438Notes

Reaction equation

HRID 2095438 reaction equation
Br[CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O.CCOC(C)=O>[CH2:17]([O:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:2][CH2:3][CH:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]2)=[CH:29][CH:30]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 3

HCID 7638MonobenzoneHCID 11430Potassium CarbonateHCID 10541625tert-Butyl 4-(2-bromoethyl)piperidine-1-carboxylate

Product 1

HCID 59371402tert-Butyl 4-[2-[4-(Benzyloxy)phenoxy]ethyl]piperidine-1-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution/suspension of tert-butyl 4-(2-bromoethyl)piperidine-1-carboxylate (1.22 g, 4.18 mmol), 4-(benzyloxy)phenol (1.01 g, 5.04 mmol, 1.20 equiv.), K2CO3 (830 mg, 6.01 mmol, 1.40 equiv.) and KI (75 mg, 0.45 mmol, 0.11 equiv.) in acetone was heated to reflux under N2 overnight. After cooling to room temperature, the mixture was diluted with 100 mL of EtOAc, and the solids were filtered off. The filtrate was concentrated under vacuum, and the residue was applied onto a silica gel column, which was eluted with ethyl acetate/petroleum ether (1:5) to afford the product (1.25 g, 73%) as a white solid. 1H NMR (CDCl3, 300 MHz) δ 7.43-7.29 (m, 5H), 6.90 (d, 2H, J=6.6 Hz), 5.01 (s, 2H), 4.08 (d, 2H, J=7.2 Hz), 3.95 (t, 1H, J=4.2 Hz), 2.70 (t, 2H, J=9.6 Hz), 1.71-1.69 (m, 5H), 1.45 (s, 9H), 1.20-1.15 (m, 2H). LC-MS (ESI) m/z 434 (M+Na+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux under N2 overnight
  3. filtrationthe solids were filtered off
  4. concentrationThe filtrate was concentrated under vacuum
  5. washwas eluted with ethyl acetate/petroleum ether (1:5)

Sources & evidence

ORD record
ord-69dbba93b05848e9b96d6d35e5ff03c6
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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