Ethyl bromoacetate → tert-Butyl (3R)-6-cyclohexyl-3-{3-[(2-ethoxy-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}hexanoate

HRID 1279871Notes

Reaction equation

HRID 1279871 reaction equation
[H-].[Na+].[CH:3]1([CH2:9][CH2:10][CH2:11][C@@H:12]([C:21]2[O:25][N:24]=[C:23]([CH2:26][OH:27])[N:22]=2)[CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>O1CCCC1.C(OCC)(=O)C>[CH:3]1([CH2:9][CH2:10][CH2:11][C@@H:12]([C:21]2[O:25][N:24]=[C:23]([CH2:26][O:27][CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[N:22]=2)[CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 59909744tert-Butyl(3R)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate

Product 1

HCID 59909756tert-Butyl (3R)-6-cyclohexyl-3-{3-[(2-ethoxy-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}hexanoateYield 63.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride 60% suspension in mineral oil (13 mg, 0.33 mmol) in anhydrous tetrahydrofuran (1 ml) was cooled to 0° C. and treated with a solution of tert-butyl (3R)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate (Preparation 85) (105 mg, 0.30 mmol) in anhydrous tetrahydrofuran (1 ml) and stirred under a nitrogen atmosphere for 1 hour. Ethyl bromoacetate (37 μl, 0.33 mmol) was added and the mixture was stirred for 18 hours, being allowed to warm to room temperature over this time. The reaction mixture was diluted with ethyl acetate and washed with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The solid was purified by column chromatography on silica gel eluting with a gradient system of pentane:ethyl acetate (99:1) to pentane:ethyl acetate (80:20) to afford the title compound as a colourless oil (84 mg).

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. temperatureto warm to room temperature over this time
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe solid was purified by column chromatography on silica gel eluting with a gradient system of pentane:ethyl acetate (99:1) to pentane:ethyl acetate (80:20)

Sources & evidence

ORD record
ord-99b10e1422a147bd987f5aed7067e9b1
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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