Tetrahydrofuran → HCID 54433767, compound

HRID 964519Notes

Reaction equation

HRID 964519 reaction equation
[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C@@H:11]([OH:26])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[NH:19][C:20](=O)[C:21]([CH3:24])([CH3:23])[CH3:22].O1CCCC1>C(Cl)Cl>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][CH:6]=[CH:5][C:4]=1[C@@H:11]([OH:26])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=1[NH:19][CH2:20][C:21]([CH3:23])([CH3:22])[CH3:24]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 54199838HCID 54199838, compound

Product 1

HCID 54433767HCID 54433767, compoundYield 99.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

A four-necked flask of 1 L capacity was charged with 60 g (0.159 mol) of (S)-α-(2,3-dimethoxyphenyl)-4-chloro-2-(pivaloylamino)benzyl alcohol, 240 ml of tetrahydrofuran, and 60 ml of methylene chloride and after the atmosphere in the flask was purged with N2 gas, the mixture was stirred with cooling at 10° C. Then, 144 ml of 70% NaAlH2 (OCH2CH2OCH3)2 (Red-Al)/toluene maintained at 10-25° C. was added dropwise under constant stirring. After completion of dropwise addition, the mixture was allowed to stand at room temperature overnight. Next morning, 100 ml of water was added dropwise under ice-cooling and stirring and the mixture was extracted with 923 ml of ethyl acetate. The aqueous layer was further extracted with 923 ml of ethyl acetate. The extracts were combined, and 100 g of anhydrous MgSO4 and 6 g of activated carbon powder for decolorization were added. The mixture was stirred for 10 minutes and, then, filtered. The residue on the filter was washed with 462 ml of ethyl acetate. The filtrate and wash were combined and concentrated under reduced pressure. By this procedure, the objective compound was obtained as a viscous oily residue. Crude yield 62.16 g (optical purity 92.9%, yield 99.6%).

Workup

  1. customafter the atmosphere in the flask was purged with N2 gas
  2. temperatureThen, 144 ml of 70% NaAlH2 (OCH2CH2OCH3)2 (Red-Al)/toluene maintained at 10-25° C.
  3. additionwas added dropwise under constant stirring
  4. additionAfter completion of dropwise addition
  5. additionNext morning, 100 ml of water was added dropwise under ice-
  6. temperaturecooling
  7. stirringstirring
  8. extractionthe mixture was extracted with 923 ml of ethyl acetate
  9. extractionThe aqueous layer was further extracted with 923 ml of ethyl acetate
  10. addition100 g of anhydrous MgSO4 and 6 g of activated carbon powder for decolorization were added
  11. stirringThe mixture was stirred for 10 minutes
  12. filtrationfiltered
  13. washThe residue on the filter was washed with 462 ml of ethyl acetate
  14. washThe filtrate and wash
  15. concentrationconcentrated under reduced pressure
  16. customBy this procedure, the objective compound was obtained as a viscous oily residue

Sources & evidence

ORD record
ord-3e4f4a0ab6544d028afdee07d89c9b5a
Source dataset
uspto-grants-1998_06
Patent number
US05770438

Reaction notes

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