Water → 1-((S)-7-Fluoro-2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)-3-methyl-3-[(S)-2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidine

HRID 2407316Notes

Reaction equation

HRID 2407316 reaction equation
[CH3:1][C@:2]1([CH2:8][O:9][CH2:10][CH2:11][O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]1.[F:19][C:20]1[CH:21]=[CH:22][C:23]2[O:28][CH2:27][C@H:26]([CH2:29]OS(C)(=O)=O)[O:25][C:24]=2[CH:35]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[F:19][C:20]1[CH:21]=[CH:22][C:23]2[O:28][CH2:27][C@H:26]([CH2:29][N:4]3[CH2:5][CH2:6][CH2:7][C:2]([CH3:1])([CH2:8][O:9][CH2:10][CH2:11][O:12][C@H:13]4[CH2:18][CH2:17][CH2:16][CH2:15][O:14]4)[CH2:3]3)[O:25][C:24]=2[CH:35]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66727215(S)-3-Methyl-3-[2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidineHCID 86644722methanesulfonic acid (R)-(7-fluoro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl ester

Product 1

HCID 667268271-((S)-7-Fluoro-2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)-3-methyl-3-[(S)-2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidineYield 23.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-3-Methyl-3-[2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidine (100 mg, 0.39 mmol), methanesulfonic acid (R)-(7-fluoro-2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl ester (102 mg, 0.39 mmol), K2CO3 (59 mg, 0.43 mmol) and KI (3 mg) were refluxed in dry DMF (3 ml) for 5 h. Water was added to the cooled mixture, followed by extraction with EtOAc (3×15 ml). The extracts were washed several times with water and finally with brine. After drying and filtering, the solvent was evaporated to give 143 mg of the crude product. This was chromatographed on silica (heptane/EtOAc, 70:30) to give 39 mg of the title compound as a colorless oil.

Workup

  1. extractionfollowed by extraction with EtOAc (3×15 ml)
  2. washThe extracts were washed several times with water
  3. customAfter drying
  4. filtrationfiltering
  5. customthe solvent was evaporated
  6. customto give 143 mg of the crude product
  7. customThis was chromatographed on silica (heptane/EtOAc, 70:30)

Sources & evidence

ORD record
ord-c085111c87de4baba1254213548db91a
Source dataset
uspto-grants-2014_08
Patent number
US08809536B2

Reaction notes

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