Sodium Hydroxide → {(S)-1-[(S)-1-(2,3-Dihydrobenzo[1,4]dioxin-2-yl)methyl]-3-methylpiperidin-3-ylmethoxy}acetic acid tert-butyl ester

HRID 453816Notes

Reaction equation

HRID 453816 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[CH2:11][N:12]1[CH2:17][CH2:16][CH2:15][C@@:14]([CH2:19][OH:20])([CH3:18])[CH2:13]1.[OH-].[Na+].[C:23]([O:27][C:28](=[O:31])[CH2:29]Br)([CH3:26])([CH3:25])[CH3:24]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:23]([O:27][C:28](=[O:31])[CH2:29][O:20][CH2:19][C@@:14]1([CH3:18])[CH2:15][CH2:16][CH2:17][N:12]([CH2:11][C@@H:2]2[O:1][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[O:4][CH2:3]2)[CH2:13]1)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 25176123{(S)-1-[(S)-1-(2,3-Dihydrobenzo[1,4]dioxin-2-yl)methyl]-3-methylpiperidin-3-yl}methanol

Product 1

HCID 66727297{(S)-1-[(S)-1-(2,3-Dihydrobenzo[1,4]dioxin-2-yl)methyl]-3-methylpiperidin-3-ylmethoxy}acetic acid tert-butyl esterYield 68.1%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To a stirred solution of {(S)-1-[(S)-1-(2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]-3-methylpiperidin-3-yl}methanol (0.516 g, 1.8 mmol) in toluene (4 ml) was added tetrabutylammonium bromide (0.12 g) and 50% NaOH (4 ml). The mixture was stirred at RT for 15 min and bromoacetic acid tert-butyl ester (0.53 g) was added. After vigorous stirring at RT overnight, the reaction was quenched by addition of brine (15 ml) and the aqueous phase extracted twice with toluene. The combined organic phases were extracted with 1 M HCl solution and the acidic water phase was basified by addition of NaOH. Extraction with toluene and evaporation afforded the title compound (0.48 g) as an oil.

Workup

  1. stirringAfter vigorous stirring at RT overnight
  2. customthe reaction was quenched by addition of brine (15 ml)
  3. extractionthe aqueous phase extracted twice with toluene
  4. extractionThe combined organic phases were extracted with 1 M HCl solution
  5. additionthe acidic water phase was basified by addition of NaOH
  6. extractionExtraction
  7. customwith toluene and evaporation

Sources & evidence

ORD record
ord-38c150dcfd8f4d54a8c5d70c22fbbf8a
Source dataset
uspto-grants-2013_07
Patent number
US08492549B2

Reaction notes

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