Water → (S)-1-Benzyl-3-methyl-3-[2-(tetrahydropyran-2-yloxy)ethoxymethyl]piperidine

HRID 2366027Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@@:10]([CH2:15][OH:16])([CH3:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:18][CH2:19][O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1.O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+].[Cl-].[Na+].O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@:10]([CH3:14])([CH2:15][O:16][CH2:18][CH2:19][O:20][CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][O:22]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

(S)-(1-Benzyl-3-methylpiperidin-3-yl)methanol (1.29 g, 5.9 mmol) and tetrabutylammonium bromide (0.19 g, 0.59 mmol) were stirred in 50% NaOH (40 ml) for 15 min. The mixture was then heated to 60° C. and 2-(2-bromoethoxy)tetrahydropyran (2.7 ml, 17.7 mmol) was slowly added (2 h) from a dropping funnel. Stirring was then continued for 4 h at 60° C. Water (40 ml) and brine (20 ml) were added to the cooled mixture, which was extracted with toluene (3×50 ml). The combined extracts were washed twice with water and brine, dried, filtered and evaporated to give 3.0 g of the crude product mixture, which was subjected to flash chromatography on silica. Elution with heptane/EtOAc (80:20) gave 1.14 g of the title compound as a colorless oil.

Workup

extractionwas extracted with toluene (3×50 ml)
washThe combined extracts were washed twice with water and brine
customdried
filtrationfiltered
customevaporated
customto give 3.0 g of the crude product mixture, which
washElution with heptane/EtOAc (80:20)

Sources & evidence

ORD record: ord-af9acdd918f04ff392eb04ae12f422e1
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697723B2

Reaction notes

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