(S)-tert-Butyl 4-(tert-butoxycarbonylamino)-5-(methoxy(methyl)amino)-5-oxopentanoate → (S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate

HRID 1782184Notes

Reaction equation

HRID 1782184 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19](N(OC)C)=[O:20])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:25]([Mg]Br)=[CH2:26]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:19](=[O:20])[CH:25]=[CH2:26])[CH2:10][CH2:11][C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 10665266(S)-tert-Butyl 4-(tert-butoxycarbonylamino)-5-(methoxy(methyl)amino)-5-oxopentanoateHCID 178418507HCID 178418507, compound

Product 1

HCID 86608878(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

(S)-tert-Butyl 4-(tert-butoxycarbonylamino)-5-(methoxy(methyl)amino)-5-oxopentanoate (4.12 g, 12.2 mmol) was dissolved in anhydrous tetrahydrofuran (100 mL) and cooled to −70° C. under nitrogen. Vinylmagnesium bromide (37 mL, 1.0 M soln in THF, 3.0 eq) was added dropwise. The reaction stirred for 30 min at −70° C. and was then the cooling bath was removed and the reaction stirred at room temperature overnight. The mixture was colled on in an ice bath and acetic anhydride (20 mL) was added, followed by methanol (27 mL). The mixture was concentrated under pressure to a small volume and then diluted with ethyl acetate. The reaction mixture was washed successively with water and brine and dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography, on silica gel, eluting with 1:4 ethyl acetate:hexanes to yield (S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-oxohept-6-enoate (0.94 g) as a yellow oil. 1H NMR (CDCl3): 6.48-6.45 (m, 2H), 5.94 (m, 1H), 5.29 (m, 1H), 4.70 (m, 1H), 2.38-2.05 (m, 2H), 2.02 (m, 1H), 1.70 (m, 1H), 1.45 ppm (s, 18H).

Workup

  1. customthe cooling bath was removed
  2. stirringthe reaction stirred at room temperature overnight
  3. customThe mixture was colled on in an ice bath
  4. additionacetic anhydride (20 mL) was added
  5. concentrationThe mixture was concentrated under pressure to a small volume
  6. additiondiluted with ethyl acetate
  7. washThe reaction mixture was washed successively with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by flash column chromatography, on silica gel
  12. washeluting with 1:4 ethyl acetate

Sources & evidence

ORD record
ord-09cec3fa6f11486db674177703dc5958
Source dataset
uspto-grants-2009_03
Patent number
US07498353B2

Reaction notes

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