Citric Acid → HCID 86591010, compound

HRID 1373155Notes

Reaction equation

HRID 1373155 reaction equation
CS(C)=O.[C:5]([O:9][C:10]([N:12]1[CH2:23][C:22]2([OH:24])[CH:14]([O:15][C:16]3([OH:32])[CH:20]([O:21]2)[CH2:19][N:18]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:17]3)[CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].C(Cl)(=O)C(Cl)=O.C(OC(N1C[C@H](O)[C@@H](O)C1)=O)(C)(C)C.C(N(CC)CC)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[C:5]([O:9][C:10]([N:12]1[CH2:23][C:22]2([OH:24])[CH:14]([O:15][C:16]3([OH:32])[CH:20]([O:21]2)[CH2:19][N:18]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:17]3)[CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 13329885tert-butyl (3S,4S)-3,4-dihydroxypyrrolidine-1-carboxylateHCID 86591011HCID 86591011, compound

Product 1

HCID 86591010HCID 86591010, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

3a, 7a-dihydroxy-octahydro-4,8-dioxa-2,6-diaza-s-indacene-2,6-dicarboxylic acid di-tert-butyl ester Dimethyl sulfoxide (279 μl, 3.94 mmol) was added dropwise to a stirred solution of oxalyl chloride (258 μl, 2.95 mmol) in THF (10 ml) at −78° C. After 10 min (3S,4S)-3,4-dihydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (0.5 g, 2.46 mmol) [Nagel, Angew. Chem., 96, 425 (1984)] in THF (5 ml) was added. The mixture was stirred at −78° C. for 95 min, after which triethylamine (1.7 ml, 12.3 mmol) was added. Stirring was continued for a further 20 min, after which the mixture was allowed to warm to room temperature. Citric acid (5% solution) (20 ml) was added and the mixture extracted with ethyl acetate. The organic extracts were combined, dried (MgSO4), filtered, and concentrated in vacuo then purified by flash column chromatography on silica gel, eluting with 50–70% ethyl acetate in petroleum ether to give 3a, 7a-dihydroxy-octahydro-4,8-dioxa-2,6-diaza-s-indacene-2,6-dicarboxylic acid di-tert-butyl ester (195 mg, 20%); m/z (ES+) 425 (100%, [MNa]+).

Workup

  1. stirringStirring
  2. waitwas continued for a further 20 min
  3. temperatureto warm to room temperature
  4. extractionthe mixture extracted with ethyl acetate
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthen purified by flash column chromatography on silica gel
  9. washeluting with 50–70% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-9f97b0501ece4846ba4a6c2dae32687d
Source dataset
uspto-grants-2007_01
Patent number
US07160907B2

Reaction notes

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