Citric Acid → HCID 22319400, compound

HRID 497573Notes

Reaction equation

HRID 497573 reaction equation
[CH3:1][Si]([N-][Si](C)(C)C)(C)C.[Li+].[O:11]=[C:12]1[CH2:17][CH2:16][CH2:15][CH2:14][N:13]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].[NH:25]1[CH:29]=[CH:28][N:27]=[CH:26]1.C(O)(=O)C[C:32]([CH2:37][C:38]([OH:40])=O)(C(O)=O)O>O1CCCC1>[OH:40][CH:38]([C:37]1[N:25]=[CH:26][N:27]([CH2:28][CH2:29][CH3:1])[CH:32]=1)[CH:17]1[CH2:16][CH2:15][CH2:14][N:13]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:12]1=[O:11]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 795ImidazoleHCID 2733832Lithium HexamethyldisilazideHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylate

Product 1

HCID 22319400HCID 22319400, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Lithium bis(trimethylsilyl)amide (244 ml, 1M in tetrahydrofuran, 244 mmol) was added dropwise over an hour to a cooled (−75° C.) solution of tert-butyl 2-oxo-1-piperidinecarboxylate (J. Org. Chem. 1983, 48, 2424; J. Chem. Soc. I, 1989, 721) (48.7 g, 244 mmol) in tetrahydrofuran (200 ml) under nitrogen, so as to maintain the temperature below −70° C. The mixture was warmed to 0° C., stirred for 90 minutes, then re-cooled to −75° C. A solution of the imidazole from preparation 66 (26.0 g, 188 mmol) in tetrahydrofuran (86 ml) was added dropwise over 30 minutes, and once addition was complete, the reaction was stirred for 2 hours at −75° C. The mixture was poured into 15% aqueous citric acid solution (650 ml), and extracted with ethyl acetate (3×250 ml). The aqueous solution was basified to pH 8 using 10% sodium hydroxide, and extracted with dichloromethane (3×250 ml). These organic extracts were dried and concentrated under reduced pressure to give the title compound as a pale yellow solid, 54.1 g.

Workup

  1. temperatureso as to maintain the temperature below −70° C
  2. temperaturere-cooled to −75° C
  3. additionwas added dropwise over 30 minutes
  4. additiononce addition
  5. stirringthe reaction was stirred for 2 hours at −75° C
  6. extractionextracted with ethyl acetate (3×250 ml)
  7. extractionextracted with dichloromethane (3×250 ml)
  8. customThese organic extracts were dried
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6c28ac12eb164e43bf4518532cf943ba
Source dataset
uspto-grants-2005_09
Patent number
US06949577B2

Reaction notes

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