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

HRID 1279872Notes

Reaction equation

HRID 1279872 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[CH:29]([CH3:35])[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][CH:29]([CH3:35])[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 24758Sodium hydrideHCID 79040Ethyl 2-bromopropionateHCID 59909744tert-Butyl(3R)-6-cyclohexyl-3-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]hexanoate

Product 1

HCID 59909758tert-Butyl (3R)-6-cyclohexyl-3-{3-[(2-ethoxy-1-methyl-2-oxoethoxy)methyl]-1,2,4-oxadiazol-5-yl}hexanoateYield 60.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride 60% suspension in mineral oil (18 mg, 0.45 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) (142 mg, 0.40 mmol) in anhydrous tetrahydrofuran (1 ml) and stirred under a nitrogen atmosphere for 0.5 hours. Ethyl 2-bromopropionate (37 μl, 0.33 mmol) was added and the mixture was stirred for 2 days, 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 oil was purified by column chromatography on silica gel eluting with a gradient system of pentane : ethyl acetate (99:1) to pentane:ethyl acetate (0:100) to afford the title compound as a colourless oil (90 mg).

Workup

  1. stirringthe mixture was stirred for 2 days
  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 oil was purified by column chromatography on silica gel eluting with a gradient system of pentane : ethyl acetate (99:1) to pentane:ethyl acetate (0:100)

Sources & evidence

ORD record
ord-fb7dedc3681d43e7a988ce4651c3c618
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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