Ammonium Chloride → (3-Carbamoyl-5-chloro-indol-1-yl)-acetic acid tert-butyl ester

HRID 1527212ノート

反応式

HRID 1527212 の反応式
[C:1]([O:5][C:6]([CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=2)[C:11]([C:19]([OH:21])=O)=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH4+].[Cl-].C[N:25](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[CH2:8][N:9]1[C:17]2[C:12](=[CH:13][C:14]([Cl:18])=[CH:15][CH:16]=2)[C:11]([C:19](=[O:21])[NH2:25])=[CH:10]1)([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 25517Ammonium Chloride2 回HCID 81531Diisopropylethylamine2 回HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682837821-tert-Butoxycarbonylmethyl-5-chloro-1H-indole-3-carboxylic acid

生成物 1

HCID 68283031(3-Carbamoyl-5-chloro-indol-1-yl)-acetic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a mixture of 1-tert-butoxycarbonylmethyl-5-chloro-1H-indole-3-carboxylic acid (400 mg, 1.29 mmol) in CH2Cl2 (6 mL) were added successively NH4Cl (138 mg, 2.58 mmol), HBTU (1.22 g, 3.23 mmol) and DIPEA (0.902 mL, 5.17 mmol). Stirring was continued at RT for 16 h. Additional aliquots of NH4Cl (2 equiv) and DIPEA (4 equiv) were added to the reaction mixture. After stirring for 4 h, the reaction mixture was diluted with CH2Cl2 and the solution was washed with water (2×), 0.1N aqueous HCl (2×), saturated aqueous NaHCO3 (2×) and brine, dried (Phase separator) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane gradient 2:1 to 1:0) to give the title compound as a white solid. TLC Rf (EtOAc/c-hexane 2:1)=0.20; MS (LC/MS): 309 [M+H]+, 617 [2M+H]+; tR (HPLC conditions b): 4.75 min.

後処理

  1. stirringAfter stirring for 4 h
  2. washthe solution was washed with water (2×), 0.1N aqueous HCl (2×), saturated aqueous NaHCO3 (2×) and brine
  3. customdried (Phase separator)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel (EtOAc/c-hexane gradient 2:1 to 1:0)

出典と根拠

ORDレコード
ord-763d57ed96a64c9fb2b6da2f0dd59682
出典データセット
uspto-grants-2015_07
特許番号
US09085555B2

反応ノート

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