Methanol → (4s)-5-Cyclopent-1-yl-6-{(r)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethylchroman-4-ol

HRID 1516740ノート

反応式

HRID 1516740 の反応式
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[CH:12]1([C:17]2[C:26]([CH:27]([OH:38])[C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)=[C:25]([CH:39]([CH3:41])[CH3:40])[CH:24]=[C:23]3[C:18]=2[C:19](=[O:44])[CH2:20][C:21]([CH3:43])([CH3:42])[O:22]3)[CH2:16][CH2:15][CH2:14][CH2:13]1.CO>O1CCCC1>[CH:12]1([C:17]2[C:26]([C@H:27]([OH:38])[C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][CH:29]=3)=[C:25]([CH:39]([CH3:40])[CH3:41])[CH:24]=[C:23]3[C:18]=2[C@@H:19]([OH:44])[CH2:20][C:21]([CH3:42])([CH3:43])[O:22]3)[CH2:16][CH2:15][CH2:14][CH2:13]1

参加物

5

反応物 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 58002966Rac-5-cyclopent-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

生成物 1

HCID 58002963(4s)-5-Cyclopent-1-yl-6-{(r)-hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethylchroman-4-ol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

23 μl (130 μmol) of borane/N,N-diethylaniline complex are added to a solution of 0.1 mg (6.7 μmol) of (1R,2S)-1-aminoindan-2-ol in 1.0 ml of tetrahydrofuran, and the mixture is stirred for 30 min. A solution of 15 mg (33 μmol) of 5-cyclopent-1-yl-6-{hydroxy[4-(trifluormethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 38A) in 1.0 ml of tetrahydrofuran is then added dropwise, and the mixture is stirred for 2 h. Methanol is then added, and the mixture is concentrated under reduced pressure. The residue is taken up in ethyl acetate and washed in each case twice with 1 M hydrochloric acid and saturated sodium bicarbonate solution and once with saturated sodium chloride solution. The organic phase is dried over sodium sulfate and then concentrated under reduced pressure. Purification of the crude product by preparative HPLC (method 1) gives the diastereomerically pure target compounds.

後処理

  1. stirringthe mixture is stirred for 2 h
  2. concentrationthe mixture is concentrated under reduced pressure
  3. washwashed in each case twice with 1 M hydrochloric acid and saturated sodium bicarbonate solution and once with saturated sodium chloride solution
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the crude product by preparative HPLC (method 1)
  7. customgives the diastereomerically pure target compounds

出典と根拠

ORDレコード
ord-033c8cb829ea4ea3a6d02b1be5592176
出典データセット
uspto-grants-2012_07
特許番号
US08227511B2

反応ノート

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