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Ammonium Chloride → 2-{4-[(9R)-9-Hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide

HRID 579396
ノート
印刷プレビュー

反応式

HRID 579396 の反応式
[OH:1][C@@:2]1([C:34]([F:37])([F:36])[F:35])[C:14]2[CH:13]=[C:12]([O:15][CH2:16][CH2:17][CH2:18][C:19]([OH:22])([CH3:21])[CH3:20])[CH:11]=[C:10]([C:23]3[CH:24]=[N:25][N:26]([C:28]([CH3:33])([CH3:32])[C:29](O)=[O:30])[CH:27]=3)[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[Cl-].[NH4+].C([N:43](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C>CN(C)C=O.O>[OH:1][C@@:2]1([C:34]([F:37])([F:35])[F:36])[C:14]2[CH:13]=[C:12]([O:15][CH2:16][CH2:17][CH2:18][C:19]([OH:22])([CH3:21])[CH3:20])[CH:11]=[C:10]([C:23]3[CH:24]=[N:25][N:26]([C:28]([CH3:32])([CH3:33])[C:29]([NH2:43])=[O:30])[CH:27]=3)[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 1175991392-{4-[(9R)-9-Hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropionic acidHCID 178484293HCID 178484293、化合物

生成物 1

HCID 783249642-{4-[(9R)-9-Hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropanamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

Under a nitrogen atmosphere, 2-{4-[(9R)-9-hydroxy-2-(4-hydroxy-4-methylpentyloxy)-9-(trifluoromethyl)-9H-fluoren-4-yl]-1H-pyrazol-1-yl}-2-methylpropionic acid (89 mg) was dissolved in N,N-dimethylformamide (1 ml), ammonium chloride (28 mg), N,N-diisopropylethylamine (148 μl) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridin-1-ium 3-oxide hexafluorophosphate (HATU) (99 mg) were added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate (twice). The obtained organic layer was washed successively with diluted brine (twice) and saturated brine. The obtained organic layer was dried over anhydrous magnesium sulfate, the insoluble material was filtered off, and the solvent in the filtrate was evaporated. The obtained residue was purified by silica gel thin layer chromatography (a mixture of chloroform and methanol at a mixing ratio 9:1 (chloroform:methanol) was used as an elution solvent) to give the title compound (48 mg, optical purity 96.9% e.e.). The optical purity was determined under the HPLC analysis condition 2. Retention time of (R) form 13.0 min, retention time of (S) form 14.4 min.

後処理

  1. extractionthe mixture was extracted with ethyl acetate (twice)
  2. washThe obtained organic layer was washed successively with diluted brine (twice) and saturated brine
  3. dry with materialThe obtained organic layer was dried over anhydrous magnesium sulfate
  4. filtrationthe insoluble material was filtered off
  5. customthe solvent in the filtrate was evaporated
  6. customThe obtained residue was purified by silica gel thin layer chromatography (
  7. additiona mixture of chloroform and methanol at a mixing ratio 9:1 (chloroform:methanol)

出典と根拠

ORDレコード
ord-4956b61d6f374e4a81ae4860ba7c203c
出典データセット
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09040717B2

反応ノート

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