Triethylamine → Diisopropyl Ether

HRID 274605Notes

Reaction equation

HRID 274605 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.[F:37][C:38]([F:49])([F:48])[C:39]1[CH:47]=[CH:46][C:42]([C:43](Cl)=[O:44])=[CH:41][CH:40]=1>ClCCl>[CH:39]([O:29][CH:11]([CH3:12])[CH3:23])([CH3:40])[CH3:38].[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][N:20]([C:43](=[O:44])[C:42]2[CH:46]=[CH:47][C:39]([C:38]([F:37])([F:48])[F:49])=[CH:40][CH:41]=2)[CH2:19][CH2:18]1)(=[O:16])=[O:15])[CH3:13]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 186592571-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)-2-butylsulfonyl]piperazine.dihydrochloride2×

Product 2

HCID 7914Diisopropyl EtherHCID 544709291-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)-2-butylsulfonyl]-4-(4-trifluoromethylbenzoyl)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, 0.20 g) obtained in Working Example 14. To the dispersion were added, under ice-cooling, triethylamine (0.20 ml) and 4-trifluoromethylbenzoyl chloride (0.13 g). The mixture was stirred for 30 minutes at room temperatures. The reaction mixture was then concentrated under reduced pressure. The concentrate was dissolved in ethyl acetate, washed with water, dried and concentrated. The concentrate was subjected to a silica gel chromatography (eluent: hexane/ethyl acetate=1/3) for purification. The object fraction was concentrated which was processed with hydrogen chloride, followed by adding thereto isopropylether to give 1-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)-2-butylsulfonyl]-4-(4-trifluoromethylbenzoyl)piperazine (Compound 24).hydrochloride (167 mg) as colorless powder.

Workup

  1. customobtained in Working Example 14
  2. additionTo the dispersion were added, under ice-
  3. temperaturecooling
  4. concentrationThe reaction mixture was then concentrated under reduced pressure
  5. dissolutionThe concentrate was dissolved in ethyl acetate
  6. washwashed with water
  7. customdried
  8. concentrationconcentrated
  9. customThe concentrate was subjected to a silica gel chromatography (eluent: hexane/ethyl acetate=1/3) for purification
  10. concentrationThe object fraction was concentrated which
  11. additionby adding

Sources & evidence

ORD record
ord-f5fdecc8c1af49f39c425a7f6c39529f
Source dataset
uspto-grants-1995_02
Patent number
US05389663

Reaction notes

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