4-Bromophenol → 4-(4-Bromophenoxymethyl)piperidine-1-carboxylic acid isopropyl ester

HRID 423459Notes

Reaction equation

HRID 423459 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH:15][CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.[Br:29][C:30]1[CH:35]=[CH:34][C:33](O)=[CH:32][CH:31]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1.CCOCC>[Br:29][C:30]1[CH:35]=[CH:34][C:33]([O:15][CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][CH:26]([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 78084-BromophenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 57930058HCID 57930058, compound

Product 1

HCID 579303004-(4-Bromophenoxymethyl)piperidine-1-carboxylic acid isopropyl esterYield 55%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Diisopropyl azodicarboxylate (9.1 mL, 46.27 mmol) in THF (15 mL) was added dropwise to a solution of 1-methylethyl 4-(hydroxymethyl)-1-piperidinecarboxylate (7.76 g, 38.56 mmol), 4-bromophenol (6.67 g, 38.56 mmol) and Ph3P (13.15 g, 50.12 mmol) in THF (85 mL) at −20° C. The reaction mixture was allowed to warm to ambient temperature and stirred at ambient temperature overnight. The mixture was concentrated, and the residue was purified by chromatography on a silica gel column using 0 to 25% EtOAc/hexane to give the crude product. The crude product was taken up in Et2O (250 mL) and washed with 1N NaOH (aq). The organic extracts were dried over MgSO4, filtered, and the filtrate was concentrated to give 7.5 g (55%) of 1-methylethyl 4-{[(4-bromophenyl)oxy]methyl}-1-piperidinecarboxylate as a white solid. 1H NMR (400 MHz, CDCl3): δ7.35 (d, 2H, J=8.9 Hz), 6.75 (d, 2H, J=8.9 Hz), 4.96-4.83 (m, 1H), 4.24-4.14 (m, 2H), 3.75 (d, 2H, J=6.4 Hz), 2.81-2.71 (m, 2H), 2.02-1.87 (m, 1H), 1.85-1.75 (m, 2H), 1.33-1.13 (m, 8H); LRMS (ESI), m/z 356/358 (M+H).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by chromatography on a silica gel column
  3. customto give the crude product
  4. washwashed with 1N NaOH (aq)
  5. dry with materialThe organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-5bdc541666df46f994a97641ec814c6c
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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