Pyridine → HCID 22729929, compound

HRID 2085462Notes

Reaction equation

HRID 2085462 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:22]2[CH:31]=[CH:30][C:25]([C:26](NC)=O)=[CH:24][CH:23]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[NH2:53][C:54]([CH3:58])([CH3:57])[CH2:55][OH:56]>C(Cl)Cl.O>[CH2:1]([N:8]1[CH2:9][CH2:10][C:11]([C:22]2[CH:23]=[CH:24][C:25]([C:26]3[O:56][CH2:55][C:54]([CH3:58])([CH3:57])[N:53]=3)=[CH:30][CH:31]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 118072-Amino-2-methyl-1-propanolHCID 67749Trifluoromethanesulfonic anhydrideHCID 22729896HCID 22729896, compound

Product 1

HCID 22729929HCID 22729929, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-50 °C

Procedure

To a solution of 4-[1-Benzyl-4-(3-methoxy-phenyl)-piperidin-4-yl]-N-methyl-benzamide (1.01 g, 2.44 mmol), in CH2Cl2 (24 mL) was added pyridine (0.30 mL, 3.71 mmol). The reaction was cooled to −50° C. and triflic anhydride (0.45, 2.67 mmo) was added dropwise over 1 minutes. The reaction was stirred at −50° C. for 1.5 hours and at room temperature for 0.5 hours. The mixture was cooled to −50° C. and 2-amino-2-methyl propanol (0.36 mL, 3.77 mmol) was added. The reaction was allowed to warm to room temperature and stirred at room temperature for 16 hours. To the mixture was added water (5 mL) and the aqueous layer was extracted with CH2Cl2 (3×15 mL). The combined extracts were dried (MgSO4) and concentrated. Purification by flash chromatography with hexanes/EtOAc (1:1) afforded 0.75 g (68% yield) of 1-Benzyl-4-[4-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-phenyl]-4-(3-methoxy-phenyl)-piperidine. 1HNMR (400 MHz, CDCl3) δ; 7.83 (d, 2H), 7.38-7.21 (comp, 7H), 7.18 (t, 1H), 6.81-6.75 (comp, 2H), 6.63 (d, 1H), 4.08 (s, 2H), 3.78 (s, 3H), 3.41 (s, 2H), 2.79-2.40 (comp, 8H), 1.38 (s, 3H); MS (M+1) 454.2.

Workup

  1. temperatureThe mixture was cooled to −50° C.
  2. temperatureto warm to room temperature
  3. stirringstirred at room temperature for 16 hours
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3×15 mL)
  5. dry with materialThe combined extracts were dried (MgSO4)
  6. concentrationconcentrated
  7. customPurification by flash chromatography with hexanes/EtOAc (1:1)

Sources & evidence

ORD record
ord-0729b7623b8b4c1c8c332fc40cfc747e
Source dataset
uspto-grants-2004_04
Patent number
US06720336B2

Reaction notes

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