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Sodium triacetoxyborohydride → methyl 4-[(1S)-1-[[(3R)-2-(2-(4-fluorophenoxy)ethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoate

HRID 2205307
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HRID 2205307 반응식
Cl.[CH2:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][C@H:4]([C:12]([NH:14][C@H:15]([C:17]2[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=2)[CH3:16])=[O:13])[NH:3]1.[F:27][C:28]1[CH:37]=[CH:36][C:31]([O:32][CH2:33][CH:34]=O)=[CH:30][CH:29]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:27][C:28]1[CH:37]=[CH:36][C:31]([O:32][CH2:33][CH2:34][N:3]2[C@@H:4]([C:12]([NH:14][C@H:15]([C:17]3[CH:18]=[CH:19][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:25][CH:26]=3)[CH3:16])=[O:13])[CH2:5][C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:2]2)=[CH:30][CH:29]=1
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참가 물질

5

반응물 3

HCID 5049666Sodium triacetoxyborohydrideHCID 110518692-(4-Fluorophenoxy)acetaldehydeHCID 118876958methyl 4-[(1S)-1-[[(3R)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]amino]ethyl]benzoate hydrochloride

생성물 1

HCID 118876972methyl 4-[(1S)-1-[[(3R)-2-(2-(4-fluorophenoxy)ethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoate수율 54.2%

시약·촉매·용매 1

HCID 11
1,2-Dichloroethane
용매

실험 절차

To a mixture of methyl 4-[(1S)-1-[[(3R)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]amino]ethyl]benzoate hydrochloride (800 mg, 2.13 mmol) and 2-(4-fluorophenoxy)acetaldehyde (493 mg, 3.2 mmol) in 1,2-dichloroethane (10.7 mL), add sodium triacetoxyborohydride (633 mg, 2.99 mmol) and stir the mixture at room temperature overnight. Add saturated aqueous NaHCO3 (25 mL), and extract the aqueous layer with ethyl acetate (2×25 mL). Wash the combined organic layers with saturated aqueous NaCl (25 mL), dry the organic phase over MgSO4, filter, and concentrate the filtrate under reduced pressure. Subject the resulting crude material to flash chromatography on silica gel using a 0% to 60% EtOAc/hexanes gradient. Consolidate the fractions containing the product, and concentrate them under reduced pressure to furnish the title compound as a colorless foam (550 mg, 54% yield). Mass spectrum (m/z): 477 ([M+H]+).

후처리

  1. extractionAdd saturated aqueous NaHCO3 (25 mL), and extract the aqueous layer with ethyl acetate (2×25 mL)
  2. washWash the combined organic layers with saturated aqueous NaCl (25 mL)
  3. dry with materialdry the organic phase over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate the filtrate under reduced pressure
  6. additioncontaining the product
  7. concentrationconcentrate them under reduced pressure

출처 및 근거

ORD 기록
ord-8f27544b20bb4e3d952c6d338656317e
출처 데이터셋
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09371289B2

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