Toluene → HCID 86631278, compound

HRID 1260912Notes

Reaction equation

HRID 1260912 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11](C(O)=O)[C@H:10]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[CH3:24])[CH2:9]1)=[O:7])(C)(C)C.C1C=CC(P([N:39]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C(N(CC)CC)C.[OH-].[Na+].[C:51]1([CH3:57])[CH:56]=CC=C[CH:52]=1>O>[C:51]([CH:9]1[C@H:10]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[CH3:24])[C@H:11]([NH2:39])[CH2:12][CH2:13][N:8]1[C:6]([OH:5])=[O:7])([CH3:57])([CH3:56])[CH3:52]

Participants

7

Reactant 5

HCID 1140TolueneHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 57537425HCID 57537425, compound

Product 1

HCID 86631278HCID 86631278, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (3R*,4R*)-1-(tert-butoxycarbonyl)-3-(4-fluoro-2-methylphenyl)piperidine-4-carboxylic acid (4.33 g) synthesized by a known method (WO2006/004195) in toluene (24 mL) were added DPPA (5.30 g) and triethylamine (2.7 mL) at room temperature, and the mixture was stirred at 100° C. for 1 hr. The reaction mixture was cooled, 8N aqueous sodium hydroxide solution (16 mL) was added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with water and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 30→70% ethyl acetate/hexane) to give tert-butyl (3R*,4R*)-4-amino-3-(4-fluoro-2-methylphenyl)piperidine-1-carboxylic acid (3.79 g, 96%) as a pale yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled
  2. stirringthe mixture was stirred at room temperature for 3 hr
  3. extractionthe resultant product was extracted with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. customdried
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 30→70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-105bd33edd834355993e8d618aeb0e63
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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