Citric Acid → HCID 11405313, compound

HRID 2414725Notes

Reaction equation

HRID 2414725 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][CH:13]2[C:21]([OH:23])=O)(=[O:11])=[O:10])=[CH:5][CH:4]=1.ClC(OCC)=O.CN1CCOCC1.C[Si](C)(C)[O:39][NH2:40].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C(=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][CH:13]2[C:21]([NH:40][OH:39])=[O:23])(=[O:11])=[O:10])=[CH:5][CH:4]=1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 22642542HCID 22642542, compound

Product 1

HCID 11405313HCID 11405313, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

1.3 g (3.9 mmol) of the 1-(4-methoxybenzenesulfonyl)indoline-2-carboxylic acid of Example 28a are dissolved in 10 ml of N,N-dimethylacetamide (DMA) and, at −20° C., admixed successively with 0.37 ml (1 equivalent) of ethyl chloroformate and 0.81 ml of N-methylmorpholine. After an activation time of 30 minutes (min), the mixture is admixed with 3.8 ml (19.5 mmol) of O-trimethylsilylhydroxylamine and stirred at RT for a further 4 h. The mixture is diluted with ethyl acetate, acidified with citric acid and, after removal of the aqueous phase, washed with saturated NaCl solution. The organic phase is dried over sodium sulfate, filtered off and concentrated under reduced pressure. The resulting oil is subjected to chromatography under pressure over silica gel 60 using dichloromethane/ethyl acetate/acetic acid 5.5/3.5/1 as mobile phase. Product fractions (showing positive iron(III) chloride-reaction) are pooled and concentrated. The crystalline product is subsequently admixed with diethyl ether and freed of residual solvent under reduced pressure.

Workup

  1. customAfter an activation time of 30 minutes (min)
  2. customafter removal of the aqueous phase
  3. washwashed with saturated NaCl solution
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. filtrationfiltered off
  6. concentrationconcentrated under reduced pressure
  7. customProduct fractions (showing positive iron(III) chloride-reaction)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b2eecd99da2f4a0fbcb0a92edbbffb5c
Source dataset
uspto-grants-2004_11
Patent number
US06815440B2

Reaction notes

Loading…