Triethylamine → Ethyl 3-(4-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxamido)phenyl)-2-methylpropanoate

HRID 1876441ノート

反応式

HRID 1876441 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:13]([OH:15])=O)[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[CH:12]=1.FC1C(F)=C(C(O)=O)C2OC(C)(C)CC=2C=1.[NH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH:40]([CH3:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:35][CH:34]=1.C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:13]([NH:32][C:33]2[CH:34]=[CH:35][C:36]([CH2:39][CH:40]([CH3:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:37][CH:38]=2)=[O:15])[C:5]2[O:9][C:8]([CH3:10])([CH3:11])[CH2:7][C:6]=2[CH:12]=1

参加物

7

反応物 5

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 46941402Ethyl 3-(4-aminophenyl)-2-methylpropanoateHCID 585663065,6-difluoro-2,2-dimethyl-3H-benzofuran-7-carboxylic acidHCID 585664155-Fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxylic acid

生成物 1

HCID 67405616Ethyl 3-(4-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxamido)phenyl)-2-methylpropanoate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxylic acid (803) (Compound was prepared in a similar manner as that described for the synthesis of (735) (101.3 mg, 0.482 mmol) was dissolved in dichloromethane (4 mL) and ethyl 3-(4-aminophenyl)-2-methylpropanoate (646) (100 mg, 0.482 mmol), triethyl amine (0.4 mL, 2.89 mmol), and 1-propanephosphonic acid cyclic anhydride (0.34 mL, 0.58 mmol, 50% in ethyl acetate) were added and stirred overnight at room temperature. The reaction was purified in vacuo and purified by flash column chromatography on silica gel with hexanes and EtOAc to give ethyl 3-(4-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxamido)phenyl)-2-methylpropanoate. The ester was dissolved in tetrahydrofuran (1.0 mL), methanol (1.0 mL) and water (3 mL). Lithium hydroxide was added and the reaction was stirred at room temperature for 4 h. The mixture was acidified with 1M HCl and diluted with EtOAc (3 mL). The organic layer was washed with brine (3 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to yield 3-(4-(5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxamido)phenyl)-2-methylpropanoic acid (97). 1H NMR (400 MHz, CDCl3) δ 9.53 (br, 1H), 7.66 (dd, J=9.9, 2.6 Hz, 1H), 7.57 (d, J=8.4 Hz, 2H), 7.19 (d, J=8.4 Hz, 2H), 7.02 (dd, J=9.9, 2.6 Hz, 1H), 3.13-3.00 (m, 3H), 2.72 (m, 2H), 1.60 (s, 6H), 1.19 (d, J=8.0 Hz, 3H).

後処理

  1. customThe reaction was purified in vacuo
  2. custompurified by flash column chromatography on silica gel with hexanes and EtOAc

出典と根拠

ORDレコード
ord-2489883d71054ea286b39f93519ead3e
出典データセット
uspto-grants-2012_11
特許番号
US08309600B2

反応ノート

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