Ethanol → [5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester

HRID 2060346

반응식

HRID 2060346 반응식
N#N.C(O)C.Cl.[NH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1B(O)O.[CH3:17][O:18][C:19](=[O:27])[CH2:20][C:21]1[S:22][C:23](Br)=[CH:24][CH:25]=1>O.C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:17][O:18][C:19](=[O:27])[CH2:20][C:21]1[S:22][C:23]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[NH2:7])=[CH:24][CH:25]=1

참가 물질

8

반응물 4

HCID 702EthanolHCID 947NitrogenHCID 12403315Methyl 2-(5-bromothiophen-2-yl)acetateHCID 164270902-Aminophenylboronic acid hydrochloride

생성물 1

HCID 16116160[5-(2-Amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester수율 51.3%

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 962Water용매HCID 1140Toluene용매2회

반응 조건

온도
100 °C

실험 절차

(The following reaction is carried out in an N2 atmosphere.) Ethanol (3.7 mL), tetrakis-(triphenylphosphine)-palladium(0) (289 mg, 0.25 mmol) and Na2CO3 decahydrate (4.0 g, 14.0 mmol) dissolved in water (5.2 mL) are subsequently added to a solution of 2-amino-benzeneboronic acid hydrochloride (910 mg, 5.25 mmol) in toluene (52 mL). Degas the reaction mixture carefully (5 times) and flush with N2 again. A solution of (5-bromo-thiophen-2-yl)-acetic acid methyl ester (43) (1.17 g, 5.0 mmol) in toluene (4.5 mL) is added. Degas the mixture again (5 times) and stir for 22 h at 100° C. Partition the reaction solution between EtOAc and brine and extract the separated aqueous layer with EtOAc (3 times). Wash combined organic layer with water and brine and dry it with Na2SO4. Purify the crude product by preparative radial chromatography (CyH/EtOAc 5+1] to obtain [5-(2-amino-phenyl)-thiophen-2-yl]-acetic acid methyl ester (44) as a brown oil (634 mg, 51%). 1H NMR (400 MHz, CDCl3): 3.73 (s, 3H); 3.83 (s, 2H); 3.92-4.07 (br.s, 2H); 6.74 (d, 1H); 6.76 (td, 1H, J1=7.6 Hz, J2=1.3 Hz); 6.92 (d, 1H, J=3.5 Hz); 7.02 (d, 1H, J=3.5 Hz); 7.11 (td, 1H, J1=7.6 Hz, J2=1.5 Hz); 7.23 (dd, 14H, J1=7.6 Hz, J2=1.5 Hz).

후처리

  1. custom(The following reaction
  2. customDegas the reaction mixture carefully (5 times)
  3. customflush with N2 again
  4. customDegas the mixture again (5 times)
  5. customPartition the reaction solution between EtOAc and brine
  6. extractionextract the separated aqueous layer with EtOAc (3 times)
  7. washWash
  8. dry with materialdry it with Na2SO4
  9. customPurify the crude product by preparative radial chromatography (CyH/EtOAc 5+1]

출처 및 근거

ORD 기록
ord-8c0783c11b7b459eb402ec7f9cc21960
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278356B2

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