Triphenylphosphine → 4-(2-Chloro-5-iodo-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 711150Notes

Reaction equation

HRID 711150 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[OH:9].O[CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][CH:11]([O:9][C:3]2[CH:4]=[C:5]([I:8])[CH:6]=[CH:7][C:2]=2[Cl:1])[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 17144122-Chloro-5-iodophenol

Product 1

HCID 1177297854-(2-Chloro-5-iodo-phenoxy)-piperidine-1-carboxylic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-Chloro-5-iodophenol (2.50 g, 9.83 mmol), tert-butyl 4-hydroxy-1-piperidinecarboxylate (2.97 g, 14.7 mmol) and triphenylphosphine (5.15 g, 19.6 mmol), were suspended in THF (50 mL) and cooled to 0° C. Diethyl azodicarboxylate (3.08 mL, 19.6 mmol) was then added dropwise, the reaction was stirred under a N2 atmosphere for 18 h. The reaction was then partitioned between H2O and EtOAc. The organic layer was separated, washed with saturated brine, dried over MgSO4, concentrated in vacuo and subjected to FCC, eluting with 0-50% EtOAc/cyclohexane, to afford the title compound (3.43 g, 80%). (Method 3): Rt 4.98 min, m/z 337.9 [M−BOC+].

Workup

  1. customThe reaction was then partitioned between H2O and EtOAc
  2. customThe organic layer was separated
  3. washwashed with saturated brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. washeluting with 0-50% EtOAc/cyclohexane

Sources & evidence

ORD record
ord-c57fd54ed6234a84b32027cc30505acd
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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