Triphenylphosphine → 4-(7-Fluoro-3-methoxycarbonylmethyl-naphthalen-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1929583Notes

Reaction equation

HRID 1929583 reaction equation
[CH3:1][O:2][C:3](=[O:17])[CH2:4][C:5]1[CH:14]=[C:13]([OH:15])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:16])[CH:11]=2)[CH:6]=1.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28](O)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.O>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([O:15][C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([F:16])[CH:11]=3)[CH:6]=[C:5]([CH2:4][C:3]([O:2][CH3:1])=[O:17])[CH:14]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 20335012(6-Fluoro-4-hydroxy-naphthalen-2-yl)-acetic acid methyl ester

Product 1

HCID 593267504-(7-Fluoro-3-methoxycarbonylmethyl-naphthalen-1-yloxy)-piperidine-1-carboxylic acid tert-butyl esterYield 84.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (6-fluoro-4-hydroxy-naphthalen-2-yl)-acetic acid methyl ester (500 mg, 2.1 mmol), 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (640 mg, 3.2 mmol) and triphenylphosphine (840 mg, 3.2 mmol) in anhydrous tetrahydrofuran (20 ml) was added diethyl azodicarboxylate (0.5 ml, 3.2 mmol) dropwise. After being stirred under an argon atmosphere at room temperature for 4 hours, the mixture was diluted with water (15 mL), and extracted with ethyl acetate (20 mL×2). The combined organic layers were washed with brine (20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (elution with 20% ethyl acetate in hexanes) to give 4-(7-fluoro-3-methoxycarbonylmethyl-naphthalen-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (740 mg, 84%) as a pale yellow solid.

Workup

  1. extractionextracted with ethyl acetate (20 mL×2)
  2. washThe combined organic layers were washed with brine (20 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (elution with 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-77c86aa6770f417a86770d54c29d3976
Source dataset
uspto-grants-2012_05
Patent number
US08188090B2

Reaction notes

Loading…