Triethylamine → HCID 10626532, compound

HRID 1489445Notes

Reaction equation

HRID 1489445 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].C(N(CC)CC)C.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C@@:20]([OH:45])([CH2:43][OH:44])[C@H:21]([N:23]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]([F:41])([F:40])[CH:37]([F:39])[F:38])=[CH:30][CH:29]=2)[C:24]1=[O:42])[CH3:22]>C(OCC)(=O)C>[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C@@:20]([OH:45])([CH2:43][O:44][S:2]([CH3:1])(=[O:4])=[O:3])[C@H:21]([N:23]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]([F:41])([F:40])[CH:37]([F:38])[F:39])=[CH:30][CH:29]=2)[C:24]1=[O:42])[CH3:22]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 10504686HCID 10504686, compound

Product 1

HCID 10626532HCID 10626532, compoundYield 99.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Metanesulfonyl chloride (2.12 g) and triethylamine (1.87 g) were added dropwise to an ice-cooled solution of 1-[(1R,2S)-2-(2-fluorophenyl)-2,3-dihydroxy-1-methylpropyl]-3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2-imidazolidinone (5.85 g) in ethyl acetate (60 ml). The resulting mixture was stirred for 20 minutes at 0° C. and then washed with water (20 ml×2) and an aqueous sodium chloride solution (20 ml) successively. The organic layer was dried over magnesium sulfate and evaporated in vacuo to give 1-[(1R,2S)-2-(2-fluorophenyl)-2-hydroxy-3-methanesulfonyloxy-1-methylpropyl]-3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2-imidazolidinone (6.8 g) as a colorless oil. This compound (6.8 g) was dissolved in N,N-dimethylformamide (130 ml). 1H-1,2,4-Triazole (4.24 g) and potassium carbonate (16.9 g) were added to the solution. The resulting mixture was heated at 80° C. for 5 hours, and then concentrated in vacuo. The residue was diluted with ethyl acetate (200 ml) and the mixture was washed with water (40 ml×2), 1N-hydrochloric acid (40 ml×2) and an aqueous sodium chloride solution successively. The organic layer was dried over magnesium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica gel (100 g; eluent, hexane-ethyl acetate, 2:1 to 1:2) followed by recrystallization from a mixture of ethyl acetate and diisopropyl ether to give 1-[(1R,2R)-2-(2-fluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2-imidazolidinone (4.4 g, 68%) as colorless prisms.

Workup

  1. washwashed with water (20 ml×2)
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. customevaporated in vacuo

Sources & evidence

ORD record
ord-5e34d1d6f7df4752a37bd52a0a5d1d0b
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

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