3,4-Dichlorophenol → N-(tert-butoxycarbonyl)piperidine

HRID 1582065Notes

Reaction equation

[C:1]([N:8]1[CH2:13][CH2:12][CH:11](O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClC1C=C(O)C=CC=1Cl.N(C(OCC)=O)=NC(OCC)=O>C1(C)C=CC=CC=1>[C:1]([N:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution N-BOC-4-hydroxypiperidine(2.0 g, 0.01 mol), triphenylphosphine (3.68 g, 0.014 mol) and 3,4-dichlorophenol (1.96 g, 0.012 mol) in dry toluene (75 ml) [with molecular sieves, at 0° C. and under Argon] was added diethyl azodicarboxylate (2.52 ml, 0.016 mol), dropwise. The mixture was stirred for 1.5 hrs at 0° C. Filtered the solution and removed the toluene before vigorously stirring in isohexane (100 ml) and filtered the resulting suspension. The filtrate was washed with 2M aqueous NaOH (×8), dried with Na2SO4 and evaporated in vacuo. Purification of the residue on silica (eluant: 20% EtOAc/isohexane) afforded N-Boc-Piperidine, 4-(3,4-dichloropkenoxy)-(9Cl) as a yellow solid (1.96 g). 1H NMR (DMSO): 7.52 (d, 1H), 7.31 (d, 1H), 7.01 (dd, 1H), 4.62 (m, 1H), 3.65 (m, 2H), 3.15 (m, 2H), 1.88 (m, 2H), 1.53 (m, 2H), 1.40 (s, 9H), MS (ES+): 346.3 (MH+), 368.4 (MNa+).

Workup

filtrationFiltered the solution
customremoved the toluene
stirringbefore vigorously stirring in isohexane (100 ml)
filtrationfiltered the resulting suspension
washThe filtrate was washed with 2M aqueous NaOH (×8)
dry with materialdried with Na2SO4
customevaporated in vacuo
customPurification of the residue on silica (eluant: 20% EtOAc/isohexane)

Sources & evidence

ORD record: ord-ef7a8ce809014afbac4942bde90fc2b8
Source dataset: uspto-grants-2004_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06734184B1

Reaction notes

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