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Methanol → (4s)-6-[(r)-(4-Tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-chroman-4-ol

HRID 1516735
ノート
印刷プレビュー

反応式

HRID 1516735 の反応式
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[C:12]([C:16]1[CH:21]=[CH:20][C:19]([CH:22]([OH:46])[C:23]2[C:24]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=3)=[C:25]3[C:30](=[CH:31][C:32]=2[CH:33]([CH3:35])[CH3:34])[O:29][C:28]([CH3:37])([CH3:36])[CH2:27][C:26]3=[O:38])=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13].CO>O1CCCC1>[C:12]([C:16]1[CH:17]=[CH:18][C:19]([C@@H:22]([OH:46])[C:23]2[C:24]([C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)=[C:25]3[C:30](=[CH:31][C:32]=2[CH:33]([CH3:35])[CH3:34])[O:29][C:28]([CH3:36])([CH3:37])[CH2:27][C@@H:26]3[OH:38])=[CH:20][CH:21]=1)([CH3:14])([CH3:15])[CH3:13]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 887MethanolHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 58002954Rac-6-[(4-tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

生成物 1

HCID 58002936(4s)-6-[(r)-(4-Tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-chroman-4-ol

試薬・触媒・溶媒 1

HCID 8028
Tetrahydrofuran
溶媒
2 回

実験手順

220 μl (1.26 mmol) of borane/N,N-diethylaniline complex are added very slowly to a solution of 7.07 mg (50 μmol) of (1R,2S)-1-aminoindan-2-ol in 7 ml of tetrahydrofuran, and the mixture is stirred at room temperature for 30 min. A solution of 150 mg (320 μmol) of rac-6-[(4-tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (Example 27A) in 7 ml of tetrahydrofuran is then added very slowly dropwise over a period of 30 min. After a further 6 h of stirring, methanol is added and the solvent is removed 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 residue by column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1→5:1) gives the diastereomerically pure target products.

後処理

  1. stirringAfter a further 6 h of stirring
  2. customthe solvent is removed 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 residue by column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1→5:1)
  7. customgives the diastereomerically pure target products

出典と根拠

ORDレコード
ord-cb0de0878fe3461abbaa2ac09e34843a
出典データセット
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08227511B2

反応ノート

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