Triphenylphosphine → Tert-butyl 4-((6-chloropyridin-3-yl)oxy)piperidine-1-carboxylate

HRID 1049039Notes

Reaction equation

HRID 1049039 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.[C:9]([N:16]1[CH2:21][CH2:20][CH:19](O)[CH2:18][CH2:17]1)([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.CCOC(C)=O>[C:12]([O:11][C:9]([N:16]1[CH2:21][CH2:20][CH:19]([O:8][C:5]2[CH:4]=[N:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH2:18][CH2:17]1)=[O:10])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 8198212-Chloro-5-hydroxypyridineHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 86696180Tert-butyl 4-((6-chloropyridin-3-yl)oxy)piperidine-1-carboxylateYield 47.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-chloro-5-hydroxy pyridine (5.00 g, 38.60 mmol), 1-Boc-4-hydroxypiperidine (9.32 g, 46.31 mmol) and triphenyl phosphine (15.19 g, 57.90 mmol) in THF (200 mL) at 0° C. was treated dropwise with diisopropylazodicarboxylate (11.14 mL, 57.90 mmol). The mixture was stirred at room temperature for 18 hours, diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated under vacuum. Purification by silica gel column chromatography (25-40% EtOAc in petrol (40-60° C.)) gave 4-(6-chloro-pyridin-3-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (5.70 g, 47%) as a pale yellow residue. 1H NMR (300 MHz, CDCl3) δ 8.06 (d, J=2.8 Hz, 1H), 7.23-7.16 (m, 2H), 4.51-4.41 (m, 1H), 3.75-3.64 (m, 2H), 3.40-3.29 (m, 2H), 1.99-1.86 (m, 2H), 1.83-1.67 (m, 2H), 1.47 (s, 9H). LCMS (m/z, Method A) ES+ 311.1 [M+1]+.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customPurification by silica gel column chromatography (25-40% EtOAc in petrol (40-60° C.))

Sources & evidence

ORD record
ord-bf43d6ccbd6d4c6f816230d453ba0d35
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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