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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
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HRID 1516735 반응식
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]
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참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매
2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-cb0de0878fe3461abbaa2ac09e34843a
출처 데이터셋
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08227511B2

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