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Sodium Bicarbonate → {4-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-piperidin-1-yl}-benzoic acid ethyl ester

HRID 1061309
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HRID 1061309 반응식
C(OC([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)=O)C.[NH2:19][CH2:20][C@@H:21]([C:23]1[CH:24]=[CH:25][C:26]([OH:34])=[C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[CH:28]=1)[OH:22].C(O[BH-](O[C:45](=[O:47])[CH3:46])OC(=O)C)(=O)C.[Na+].[C:49](=O)(O)[O-:50].[Na+]>CN(C)C=O.C(O)(=O)C>[CH2:45]([O:47][C:49](=[O:50])[C:8]1[CH:7]=[CH:6][CH:11]=[CH:10][C:9]=1[N:12]1[CH2:13][CH2:14][CH:15]([NH:19][CH2:20][C@H:21]([OH:22])[C:23]2[CH:24]=[CH:25][C:26]([OH:34])=[C:27]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[CH:28]=2)[CH2:16][CH2:17]1)[CH3:46]
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참가 물질

7

반응물 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 12717442Ethyl 4-(4-oxopiperidin-1-yl)benzoate

생성물 1

HCID 69654607{4-[(2R)-2-Hydroxy-2-(4-hydroxy-3-methanesulfonylamino-phenyl)-ethylamino]-piperidin-1-yl}-benzoic acid ethyl ester수율 50%

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 6228Dimethylformamide용매

실험 절차

1-(4-Ethoxycarbonylphenyl)-4-piperidone (Taylor, E. C., Skotnicki, J. S. Synthesis, 1981, 606) (0.29 g, 1.2 mmol) and N-[5-(2-amino-(1R)-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide (which was obtained in Example 10) (0.29 g, 1.2 mmol) were mixed in dimethylformamide (10 mL) and then treated with sodium triacetoxyborohydride (1.01 g, 4.7 mmol) and acetic acid (0.5 mL). After stirring at room temperature under a nitrogen atmosphere for 15 hours the mixture was poured into a saturated aqueous sodium bicarbonate. The precipitate which was formed was collected and purified by silica gel chromatography (methanol/methylene chloride) to give the titled compound as a white solid (0.28 g, 50%); mp >95° C. (decomposed); 1H NMR (300 MHz, DMSO-d6) δ 1.28 (t, J=7.1 Hz, 3H), 1.30-1.55 (m, 2H), 1.80-1.95 (m, 2H), 2.55-3.50 (m, 5H), 2.92 (s, 3H), 3.75-3.90 (m, 2H), 4.22 (q, J=7.1 Hz, 2H), 6.82 (d, J=8.2Hz, 1H), 6.95 (d, J=8.9Hz, 2H), 7.00 (dd, J=8.2, 1.9Hz, 1H), 7.18 (d, J=1.9 Hz, 1H), 7.75 (d, J=8.9 Hz, 2H); MS (ES) m/z: 478.0 (MH+); HRMS Calcd. for C23H32N3O6S(MH+): 478.2006. Found: 478.2000.

후처리

  1. customThe precipitate which was formed
  2. customwas collected
  3. custompurified by silica gel chromatography (methanol/methylene chloride)

출처 및 근거

ORD 기록
ord-28fff3b780224bea8eb9d10e2aad63dc
출처 데이터셋
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06525202B2

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