1-Hydroxybenzotriazole → (3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-[(S)-2-acetyloxy-2-phenylacetyl]perhydroisoindol-4-ol

HRID 375427노트

반응식

HRID 375427 반응식
ON1C2C=CC=CC=2N=N1.[C:11]([O:14][C@@H:15]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:16]([OH:18])=O)(=[O:13])[CH3:12].Cl.[C:26]1([C:32]2([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C@@H:40]3[C@@H:36]([CH2:37][NH:38][CH2:39]3)[C@@:35]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[O:48][CH3:49])([OH:41])[CH2:34][CH2:33]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>ClCCl>[C:50]1([C:32]2([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C@@H:40]3[C@@H:36]([CH2:37][N:38]([C:16](=[O:18])[C@@H:15]([O:14][C:11](=[O:13])[CH3:12])[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:39]3)[C@@:35]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[O:48][CH3:49])([OH:41])[CH2:34][CH2:33]2)[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1

참가 물질

7

반응물 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6923379(+)-O-Acetyl-L-mandelic AcidHCID 70218598(3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)perhydroisoindol-4-ol hydrochloride

생성물 1

HCID 22858344(3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-[(S)-2-acetyloxy-2-phenylacetyl]perhydroisoindol-4-ol수율 98.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매4회

실험 절차

0.024 g of 1-hydroxybenzotriazole and 0.33 g of (S)-2-acetyloxy-2-phenylacetic acid are added to a suspension of 0.75 g of (3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)perhydroisoindol-4-ol hydrochloride in 60 cm3 of dry dichloromethane, this solution is then cooled to +5° C. and a suspension of 0.4 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 20 cm3 of dry dichloromethane is quickly added, followed by a solution of 0.63 cm3 of diisopropylethylamine in 20 cm3 of dry dichloromethane. The reaction mixture is stirred at +5° C. for 2 hours and at room temperature for 24 hours, diluted with 120 cm3 of dichloromethane, washed with 100 cm3 of water and then with 100 cm3 of an aqueous saturated solution of sodium chloride, and is dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 2.5 cm, height 39 cm) by eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (50/50 by volume) and collecting fractions of 60 cm3. Fractions 6 to 10 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.96 g of (3aS,4S,7aS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-[(S)-2-acetyloxy-2 -phenylacetyl]perhydroisoindol-4-ol is obtained in the form of a white foam.

후처리

  1. temperaturethis solution is then cooled to +5° C.
  2. additionis quickly added
  3. washwashed with 100 cm3 of water
  4. dry with materialwith 100 cm3 of an aqueous saturated solution of sodium chloride, and is dried over magnesium sulphate
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue is chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 2.5 cm, height 39 cm)
  7. washby eluting under a pressure of 0.5 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (50/50 by volume)
  8. customcollecting fractions of 60 cm3
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

출처 및 근거

ORD 기록
ord-1f18662a8aac4141a166e4c03f8d158b
출처 데이터셋
uspto-grants-1996_01
특허 번호
US05484804

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