Acetic Anhydride → 1-acetyl-4-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)-2-butylsulfonyl]piperazine

HRID 274606Notes

Reaction equation

HRID 274606 reaction equation
Cl.Cl.[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C@@:11]([OH:29])([CH2:23][N:24]1[CH:28]=[N:27][CH:26]=[N:25]1)[C@H:12]([S:14]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)(=[O:16])=[O:15])[CH3:13].C(N(CC)CC)C.[C:37](OC(=O)C)(=[O:39])[CH3:38]>ClCCl>[C:37]([N:20]1[CH2:21][CH2:22][N:17]([S:14]([C@@H:12]([C@:11]([C:5]2[CH:6]=[CH:7][C:8]([F:10])=[CH:9][C:4]=2[F:3])([OH:29])[CH2:23][N:24]2[CH:28]=[N:27][CH:26]=[N:25]2)[CH3:13])(=[O:16])=[O:15])[CH2:18][CH2:19]1)(=[O:39])[CH3:38]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 186592571-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)-2-butylsulfonyl]piperazine.dihydrochloride2×

Product 1

HCID 543976661-acetyl-4-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)-2-butylsulfonyl]piperazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In dichloromethane (10 ml) was dispersed 1[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H ,1,2,4-triazol-1-yl)-2-butylsulfonyl]piperazine.dihydrochloride (Compound 20, 0.40 g) obtained in Working Example 14. To the dispersion were added, under ice-cooling, triethylamine (0.40 ml) and acetic anhydride (0.13 g). The mixture was stirred for 30 minutes under ice-cooling. The reaction mixture was then washed with water, dried and concentrated. The concentrated was subjected to a silica gel chromatography (eluent: dichloromethane/methanol=20/1) for purification. The object fraction was concentrated and processed with hydrogen chloride, followed by addition of isopropyl ether to give 1-acetyl-4-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)-2-butylsulfonyl]piperazine (Compound 25).hydrochloride (336 mg) as colorless powder.

Workup

  1. customobtained in Working Example 14
  2. additionTo the dispersion were added, under ice-
  3. temperaturecooling
  4. temperaturecooling
  5. washThe reaction mixture was then washed with water
  6. customdried
  7. concentrationconcentrated
  8. customThe concentrated was subjected to a silica gel chromatography (eluent: dichloromethane/methanol=20/1) for purification
  9. concentrationThe object fraction was concentrated
  10. additionfollowed by addition of isopropyl ether

Sources & evidence

ORD record
ord-5c8c0fb5637c44cba797e0eeff7bede7
Source dataset
uspto-grants-1995_02
Patent number
US05389663

Reaction notes

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