Formaldehyde → ((2-Chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-methylamino)-acetic acid ethyl ester

HRID 2250470노트

반응식

HRID 2250470 반응식
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][NH:6][C:7]1[CH:12]=[C:11]([C:13]2[N:17]=[C:16]([C:18]3[S:19][CH:20]=[CH:21][C:22]=3[Cl:23])[O:15][N:14]=2)[CH:10]=[CH:9][C:8]=1[Cl:24])[CH3:2].C=O.[C:28]([BH3-])#N.[Na+].[OH-].[Na+]>C(O)(=O)C>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][N:6]([C:7]1[CH:12]=[C:11]([C:13]2[N:17]=[C:16]([C:18]3[S:19][CH:20]=[CH:21][C:22]=3[Cl:23])[O:15][N:14]=2)[CH:10]=[CH:9][C:8]=1[Cl:24])[CH3:28])[CH3:2]

참가 물질

6

반응물 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 16222810(2-Chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenylamino)-acetic acid ethyl ester

생성물 1

HCID 16222813((2-Chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenyl}-methylamino)-acetic acid ethyl ester수율 97.2%

시약·촉매·용매 1

HCID 176Acetic Acid용매

실험 절차

To a yellow mixture of (2-chloro-5-[5-(3-chlorothiophene-2-yl)-[1,2,4]oxadiazol-3-yl]-phenylamino)-acetic acid ethyl ester (0.360 g, 0.903 mmol), paraformaldehyde (0.271 g, 9.03 mmol) and glacial acetic acid (4.5 mL) was added sodium cyanoborohydride (0.284 g, 4.51 mmol) in small portions over 5 min. The yellow mixture became a white suspension and was stirred overnight at room temperature. The white suspension was added to a 25% NaOH(aq) solution at 0° C. The aqueous layer was extracted with dichloromethane (50 mL), washed with brine (15 mL), dried over MgSO4, filtered and concentrated in vacuo. The clear oil was purified by flash column chromatography (silica gel, elution with EtOAc:hexanes, 1:5) to yield 0.362 g (96%) of the title compound as a white solid. 1H NMR (CDCl3): 7.94 (d, 1H, J=1.7 Hz), 7.73 (td, 1H, J=8.2, 1.9 and 1.7 Hz), 7.61 (dd, 1H, J=5.5, 5.2, 1.6 and 1.4 Hz), 7.45 (dd, 1H, J=8.5 and 1.4 Hz), 7.13 (dd, 1H, J=5.5, 5.2, 1.6 and 1.4 Hz), 4.18 (q, 2H, J=7.1 Hz), 4.04 (s, 2H), 3.07 (s, 3H), 1.26 (t, 3H, J=7.1 Hz).

후처리

  1. extractionThe aqueous layer was extracted with dichloromethane (50 mL)
  2. washwashed with brine (15 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe clear oil was purified by flash column chromatography (silica gel, elution with EtOAc:hexanes, 1:5)

출처 및 근거

ORD 기록
ord-9fbae5dfa2854bf0b964b1b619ddbb62
출처 데이터셋
uspto-grants-2008_01
특허 번호
US07317029B2

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