Ammonium Chloride → 1,1-Dimethylethyl 4-[(6-chloro-5-methoxy-4-pyrimidinyl)oxy]-1-piperidinecarboxylate

HRID 1811575Notes

Reaction equation

HRID 1811575 reaction equation
Cl[C:2]1[C:7]([O:8][CH3:9])=[C:6]([Cl:10])[N:5]=[CH:4][N:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].CC(C)([O-])C.[K+].[Cl-].[NH4+]>C1COCC1>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:2]2[C:7]([O:8][CH3:9])=[C:6]([Cl:10])[N:5]=[CH:4][N:3]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 787204,6-Dichloro-5-methoxypyrimidineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 584877511,1-Dimethylethyl 4-[(6-chloro-5-methoxy-4-pyrimidinyl)oxy]-1-piperidinecarboxylateYield 94.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4,6-dichloro-5-methoxy-pyrimidine (5.62 g, 27.9 mmol) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (5.02 g, 27.9 mmol) in 200 mL THF was chilled to 0° C. A 1.0 M solution of potassium t-butoxide (30.7 mL, 30.7 mmol) was added drop-wise with stirring and the resulting mixture then was allowed to stir at 0° C. for one hour. Saturated ammonium chloride (100 mL) was added and the solution extracted with ethyl acetate. The organic phase was washed with brine and dried with magnesium sulfate, solvent removed to yield 9.10 g (94.8% yield). 1HNMR (CDCl3, 400 MHz) a 1.48 (s, 2H), 1.79-1.83 (m, 2H), 1.99-2.04 (m, 2H), 3.33-3.39 (m, 2H), 3.72-3.77 (m, 2H), 3.91 (s, 3H), 5.30-5.38 (m, 1H), 8.26 (s, 1H). Exact mass calculated for C15H22ClN3O4: 343.13. found: 344.3 (MH+).

Workup

  1. stirringto stir at 0° C. for one hour
  2. extractionthe solution extracted with ethyl acetate
  3. washThe organic phase was washed with brine
  4. dry with materialdried with magnesium sulfate, solvent
  5. customremoved
  6. customto yield 9.10 g (94.8% yield)

Sources & evidence

ORD record
ord-1e5fa21f2b2143c493707d171012534f
Source dataset
uspto-grants-2013_01
Patent number
US08362248B2

Reaction notes

Loading…