Sodium hydride → (Z)-(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl ester

HRID 1473722Notes

Reaction equation

HRID 1473722 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH:5](P(OCC)(OCC)=O)[CH2:6][CH2:7][CH2:8][O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:2].[H-].[Na+].[C:28]([O:32][C:33]([NH:35][C@@H:36]([CH2:44][CH:45]=O)[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:34])([CH3:31])([CH3:30])[CH3:29]>C1COCC1>[CH2:1]([O:3][C:4](=[O:25])/[C:5](/[CH2:6][CH2:7][CH2:8][O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[CH:45]\[CH2:44][C@H:36]([NH:35][C:33]([O:32][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:34])[C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[CH3:2].[CH2:1]([O:3][C:4](=[O:25])/[C:5](/[CH2:6][CH2:7][CH2:8][O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[CH:45]/[CH2:44][C@H:36]([NH:35][C:33]([O:32][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:34])[C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 10901762tert-Butyl (S)-2-((tert-butoxycarbonyl)amino)-4-oxobutanoateHCID 866784385-Benzyloxy-2-(diethoxyphosphoryl)-pentanoic acid ethyl ester

Product 2

HCID 86678436(Z)-(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl esterHCID 86678437(E)-(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 5-Benzyloxy-2-(diethoxyphosphoryl)-pentanoic acid ethyl ester (1.36 g, 3.65 mmol) in dry THF (5 mL) was added dropwise at 0° C. to a solution of sodium hydride (0.18 g, 7.46 mmol) in dry THF (3 mL). After stirring for 15 min tert-Butyl (2S)-2-[(tert-butoxycarbonyl)amino]-4-oxobutanoate (Example 1c) (1.0 g, 3.66 mmol) was added as a solution in dry THF (5 mL) dropwise to the reaction mixture. After stirring for 90 min at 0° C. the reaction was quenched by addition of saturated sodium bicarbonate solution (50 mL). After phase separation the aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined organic layers were dried over sodium sulphate, concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (hexane/ethyl acetate gradient) to give (Z)—(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl ester and (E)-(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl ester as a mixture of diastereomers.

Workup

  1. customwas quenched by addition of saturated sodium bicarbonate solution (50 mL)
  2. customAfter phase separation the aqueous layer
  3. extractionwas extracted with ethyl acetate (3×50 mL)
  4. dry with materialthe combined organic layers were dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customthe residue was purified by column chromatography on silica gel (hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-9cdecbfb7b164a61a890bd850fe75b96
Source dataset
uspto-grants-2015_04
Patent number
US09017645B2

Reaction notes

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