Diethyl Ether → HCID 67460297, compound

HRID 554146Notes

Reaction equation

HRID 554146 reaction equation
[OH:1][C@@:2]1([CH3:20])[C:7](=[N:8][CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]2[CH2:17][C@@H:3]1[C:4]2([CH3:19])[CH3:18].C[Mg]Br.C(OCC)C.N12CCCN=C1CCCCC2.[C:40]([O:45][CH2:46][CH3:47])(=[O:44])/[CH:41]=[CH:42]/[CH3:43]>O1CCCC1>[OH:1][C@@:2]1([CH3:20])[C:7](=[N:8][C@H:9]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH:42]([CH3:43])[CH2:41][C:40]([O:45][CH2:46][CH3:47])=[O:44])[CH2:6][C@H:5]2[CH2:17][C@@H:3]1[C:4]2([CH3:19])[CH3:18]

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 429065Ethyl trans-crotonateHCID 10880518HCID 10880518, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 67460297HCID 67460297, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

A solution of 1,1-dimethylethyl N-[(1R,2R,5R)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]hept-3-ylidene]glycinate (11.05 g, 39.3 mmol) in anhydrous tetrahydrofuran (100 ml) was cooled to −30° C. and treated with a 3M solution of methylmagnesium bromide in diethyl ether (17.1 ml, 51.1 mmol). 1,8-Diazabicyclo[5.4.0]undec-7-ene (7.78 g, 51.1 mmol) was then added and the mixture was stirred for an additional 20 minutes at −30° C. The mixture was then treated with ethyl crotonate and stirring continued for 1 hr. The mixture was quenched by addition of saturated aqueous ammonium chloride solution (35 ml) and then extracted with ethyl acetate (3×100 ml). The combined organic extracts were dried over sodium sulphate, filtered and evaporated to give a yellow oil. This material was purified by automated flash silica-gel column chromatography (using a Biotage SP4), eluting with a gradient of 0-20% (over 5 column volumes) then 20-35% (over 14 column volumes) ethyl acetate in hexane, to give 1-(1,1-dimethylethyl) 5-ethyl N-[(1R,2R,5R)-2-hydroxy-2,6,6-trimethylbicyclo[3.1.1]hept-3-ylidene]-3-methylglutamate (4.2 g) which was used in the next step.

Workup

  1. stirringstirring
  2. waitcontinued for 1 hr
  3. customThe mixture was quenched by addition of saturated aqueous ammonium chloride solution (35 ml)
  4. extractionextracted with ethyl acetate (3×100 ml)
  5. dry with materialThe combined organic extracts were dried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customto give a yellow oil
  9. customThis material was purified by automated flash silica-gel column chromatography (
  10. washeluting with a gradient of 0-20% (over 5 column volumes)

Sources & evidence

ORD record
ord-d5994b12f4a34fcea9d92d1b575eb8f9
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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