N-(9-Fluorenylmethoxycarbonyloxy)succinimide → (S)-2-[1-(9-fluorenylmethyloxycarbonyl)-6-oxo-1,7-diazaspiro[4.4]non-7-yl]propionic acid

HRID 276758Notes

Reaction equation

HRID 276758 reaction equation
C(=O)(O)[O-].[Na+].[O:6]=[C:7]1[N:15]([C@@H:16]([CH3:20])[C:17]([OH:19])=[O:18])[CH2:14][CH2:13][C:8]21[NH:12][CH2:11][CH2:10][CH2:9]2.[C:21](=O)([O:37]N1C(=O)CCC1=O)[O:22][CH2:23][CH:24]1[C:36]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:30]2[C:25]1=[CH:26][CH:27]=[CH:28][CH:29]=2>O.CC(C)=O>[CH:35]1[C:36]2[CH:24]([CH2:23][O:22][C:21]([N:12]3[C:8]4([CH2:13][CH2:14][N:15]([C@@H:16]([CH3:20])[C:17]([OH:19])=[O:18])[C:7]4=[O:6])[CH2:9][CH2:10][CH2:11]3)=[O:37])[C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]=2[CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 54078033(S)-2-(6-oxo-1,7-diazaspiro[4.4]non-7-yl)propionic acid

Product 1

HCID 53806324(S)-2-[1-(9-fluorenylmethyloxycarbonyl)-6-oxo-1,7-diazaspiro[4.4]non-7-yl]propionic acidYield 72.1%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent2×

Procedure

Excess solid sodium bicarbonate was added to (S)-2-(6-oxo-1,7-diazaspiro[4.4]non-7-yl)propionic acid (0.42 g) in water (2 ml) and then 9-fluorenylmethyl succinimidyl carbonate (0.7 g) in acetone (3 ml) was added. The mixture was stirred for 18 hours. The mixture was then added to water (10 ml), extracted with ether (10 ml) and the aqueous layer separated. (The ether extracts were discarded). The pH of the aqueous layer was adjusted to ˜3 with concentrated hydrochloric acid and then it was extracted with dichloromethane (2×10 ml). The combined extracts were separated, dried (MgSO4) and evaporated to give (S)-2-[1-(9-fluorenylmethyloxycarbonyl)-6-oxo-1,7-diazaspiro[4.4]non-7-yl]propionic acid (0.62 g) as a white foam; NMR (d6-DMSO (373K)): some doubling of peaks due to the mixture of diastereoisomers, 1.3 (2d, 3H), 1.6-2.0 (m, 6H), 3.05 (m, 1H), 3.2-3.45 (m, 3H) 4.2-4.4 (m, 1H), 4.5 (m, 1H), 6.2 (s, 2H), 7.35 (m, 4H), 7.8 (m, 4H).

Workup

  1. extractionextracted with ether (10 ml)
  2. customthe aqueous layer separated
  3. extractionit was extracted with dichloromethane (2×10 ml)
  4. customThe combined extracts were separated
  5. dry with materialdried (MgSO4)
  6. customevaporated

Sources & evidence

ORD record
ord-a2bbe3b5039243feaedd78b2ebc16055
Source dataset
uspto-grants-2002_03
Patent number
US06355617B1

Reaction notes

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