1,2-Dichloroethane → HCID 59753381, compound

HRID 751762Notes

Reaction equation

HRID 751762 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12](C(O)=O)[CH2:13][O:14][C:15]([C@@H:17]1[CH2:21][C@@H:20]([CH3:22])[CH2:19][N:18]1[C:23](=[O:49])[C@@H:24]([NH:26][C:27]([C@@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][N:30]1[C:35]([C@@H:37]1[CH2:41][CH2:40][CH2:39][N:38]1[C:42](OC(C)(C)C)=[O:43])=[O:36])=[O:28])[CH3:25])=[O:16])=[O:10])C1C=CC=CC=1.F[C:54]1[C:59](O)=[C:58](F)[C:57](F)=[C:56](F)[C:55]=1F.C(Cl)CCl>ClCCl>[CH3:22][C@H:20]1[CH2:19][N:18]2[C@H:17]([C:15](=[O:16])[O:14][CH2:13][C@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:42](=[O:43])[N:38]3[C@H:37]([C:35](=[O:36])[N:30]4[C@H:29]([C:27](=[O:28])[NH:26][C@@H:24]([CH3:25])[C:23]2=[O:49])[CH2:34][CH2:33][CH2:32][CH2:31]4)[CH2:41][CH2:40][CH2:39]3)[CH2:21]1

Participants

5

Reactant 3

HCID 111,2-DichloroethaneHCID 13041PentafluorophenolHCID 86598032HCID 86598032, compound

Product 1

HCID 59753381HCID 59753381, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

3.95 g (5.41 mm ol) of the acid from example 25A and 3.98 g (21.65 mmol) of pentafluorophenol are dissolved in dichloromethane (13 ml) and cooled to −20° C. under argon. 1.14 g (5.95 mmol) of EDC are added, and the reaction mixture is stirred overnight with slow warming to RT. The reaction solution is concentrated to dryness and the residue is treated at 0° C. with 4N hydrogen chloride solution in dioxane (80 ml). The mixture is stirred for 3 h and the solvent is subsequently removed in vacuo. The residue is dissolved in dichloromethane (about 900 ml) and slowly added dropwise at RT to a vigorously stirred two-phase mixture of 1N aqueous sodium hydrogencarbonate solution (700 ml) and dichloromethane (1200 ml). The reaction mixture is stirred overnight. The phases are separated, the aqueous phase is extracted three times with dichloromethane and the combined organic phases are dried over sodium sulfate, filtered and concentrated to dryness. The residue (2.7 g of yellow hard foam) is purified by chromatography in 3 portions by means of preparative RP-HPLC using acetonitrile/water (gradient). 1.98 g (60% of th.) of the product are obtained.

Workup

  1. temperaturewith slow warming to RT
  2. concentrationThe reaction solution is concentrated to dryness
  3. additionthe residue is treated at 0° C. with 4N hydrogen chloride solution in dioxane (80 ml)
  4. stirringThe mixture is stirred for 3 h
  5. customthe solvent is subsequently removed in vacuo
  6. dissolutionThe residue is dissolved in dichloromethane (about 900 ml)
  7. additionslowly added dropwise at RT to a vigorously stirred two-phase mixture of 1N aqueous sodium hydrogencarbonate solution (700 ml) and dichloromethane (1200 ml)
  8. stirringThe reaction mixture is stirred overnight
  9. customThe phases are separated
  10. extractionthe aqueous phase is extracted three times with dichloromethane
  11. dry with materialthe combined organic phases are dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated to dryness
  14. customThe residue (2.7 g of yellow hard foam) is purified by chromatography in 3 portions by means of preparative RP-HPLC
  15. custom1.98 g (60% of th.) of the product are obtained

Sources & evidence

ORD record
ord-9efe8c7fdb904e92a58444f8e299a5de
Source dataset
uspto-grants-2008_07
Patent number
US07405201B2

Reaction notes

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