Pyridine → HCID 19966157, compound

HRID 977885Notes

Reaction equation

HRID 977885 reaction equation
Cl[C:2]([O:4][C:5](Cl)(Cl)Cl)=[O:3].N1C=CC=CC=1.[C:15]([C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][CH:27]([OH:35])[CH2:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:21][C:20]=1[NH:36][C:37](=[O:53])[CH2:38][CH:39]1[C:52]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[O:46][C:45]2[C:40]1=[CH:41][CH:42]=[CH:43][CH:44]=2)([CH3:18])([CH3:17])[CH3:16].OC[C:56]([O:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)=[O:57]>O1CCCC1.C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:15]([C:19]1[CH:24]=[CH:23][C:22]([CH2:25][CH2:26][CH:27]([O:35][C:2]([O:4][CH2:5][C:56]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[O:57])=[O:3])[CH2:28][CH:29]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]2)=[CH:21][C:20]=1[NH:36][C:37](=[O:53])[CH2:38][CH:39]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:45]=2[O:46][C:47]2[C:52]1=[CH:51][CH:50]=[CH:49][CH:48]=2)([CH3:18])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 1049PyridineHCID 10426DiphosgeneHCID 561337Benzyl 2-hydroxyacetateHCID 19966195HCID 19966195, compound

Product 1

HCID 19966157HCID 19966157, compoundYield 158.1%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 55 μl (0.46 mmol) of trichloromethyl chloroformate in 1 ml of tetrahydrofuran was added dropwise to a solution of 74 μl (0.91 mmol) of pyridine in 1 ml of tetrahydrofuran, whilst ice-cooling, and then the temperature of the resulting mixture was allowed to rise gradually to room temperature. The mixture was stirred for 1 hour at room temperature, after which it was again cooled, and a solution of 400 mg (0.76 mmol) of N-[2-t-butyl-5-(4-cyclohexyl-3-hydroxybutyl)phenyl]-2-(9H-xanthen-9-yl)acetamide (prepared as described in Example 12) in 3 ml of tetrahydrofuran was added dropwise. The mixture was stirred for 1 hour at the same temperature, and then the solvent was removed by distillation under reduced pressure, to give a colorless foam-like material as a residue. This residue was dissolved in 1 ml of methylene chloride, and a solution of 151 mg (0.91 mmol) of benzyl α-hydroxyacetate in 1.5 ml of methylene chloride and then 110 mg (0.91 mmol) of 4-(N,N-dimethylamino)pyridine were added dropwise, whilst ice-cooling. The mixture was stirred at room temperature for 1 hour, and then the reaction mixture was diluted with methylene chloride, after which it was washed with water and with a saturated aqueous solution of sodium chloride, in that order. The organic phase was dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through 75 g of silica gel, using a 1:9 by volume mixture of methylene chloride and ethyl acetate as the eluent, to give 522 mg (yield 96%) of the title compound as a colorless foam-like material.

Workup

  1. temperaturecooling
  2. customto rise gradually to room temperature
  3. temperatureafter which it was again cooled
  4. stirringThe mixture was stirred for 1 hour at the same temperature
  5. customthe solvent was removed by distillation under reduced pressure
  6. customto give a colorless foam-like material as a residue
  7. temperaturecooling
  8. stirringThe mixture was stirred at room temperature for 1 hour
  9. washafter which it was washed with water and with a saturated aqueous solution of sodium chloride, in that order
  10. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  11. customthe solvent was removed by distillation under reduced pressure
  12. customThe resulting residue was purified by column chromatography through 75 g of silica gel
  13. additionby volume mixture of methylene chloride and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-e742fd8332234f598efdb369f15c7250
Source dataset
uspto-grants-1997_03
Patent number
US05614550

Reaction notes

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