Potassium Carbonate → 4-{6-[2-fluoro-4-(2-hydroxy-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl Ester

HRID 2377942Notes

Reaction equation

HRID 2377942 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C([Si](C)(C)[O:27][CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[C:32]([F:37])[CH:31]=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.C1COCC1.O>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([O:36][C:33]3[CH:34]=[CH:35][C:30]([CH2:29][CH2:28][OH:27])=[CH:31][C:32]=3[F:37])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2724141Tetrabutylammonium FluorideHCID 114933574-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl esterHCID 672032794-[2-(Tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-phenol

Product 1

HCID 598567524-{6-[2-fluoro-4-(2-hydroxy-ethyl)-phenoxy]-5-methyl-pyrimidin-4-yloxy}-piperidine-1-carboxylic Acid Isopropyl EsterYield 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (270 mg, 0.84 mmol) and 4-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-phenol (279 mg, 0.84 mmol) in DMF (5 mL), was K2CO3 (137 mg, 0.84 mmol) added. The reaction mixture was irradiated under microwave for 1 hour at 150° C. The reaction was cooled to room temperature and treated with 1.0 M TBAF in THF (0.9 mL). After stirring for 2 hours, the reaction was poured into H2O (50 mL) and extracted with ethyl acetate (50 mL). The ethyl acetate was dried over MgSO4, and concentrated under vacuum and purified over SiO2 to afford the desired compound (321 mg, 89%) as a white solid. 1H NMR (400 Mz, DMSO-d6) δ 8.21 (s, 1H), 7.38˜7.37 (m, 1H), 7.29˜7.28 (m, 1H), 7.21˜7.17 (m, 1H), 5.30 (m, 1H), 4.75 (m, 1H), 3.67˜3.65 (m, 2H), 3.64˜3.41 (m, 2H), 3.33˜3.30 (m, 2H), 3.02 (m, 2H), 2.91 (s, 3H), 1.99˜1.93 (m, 2H), 1.66˜1.64 (m, 2H), 1.22 (d, 6H). LCMS 432.6 [MH+].

Workup

  1. additionadded
  2. customThe reaction mixture was irradiated under microwave for 1 hour at 150° C
  3. extractionextracted with ethyl acetate (50 mL)
  4. dry with materialThe ethyl acetate was dried over MgSO4
  5. concentrationconcentrated under vacuum
  6. custompurified over SiO2

Sources & evidence

ORD record
ord-9fab3e8daec140f8b35cbdc2531fdf75
Source dataset
uspto-grants-2008_12
Patent number
US07470699B2

Reaction notes

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