Anthranilic Acid → 2-[(2,5-Dichloro-4-pyridinyl)amino]benzoic acid

HRID 1472531

反応式

HRID 1472531 の反応式
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=[O:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2OC2C=CC=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([NH:10][C:11]2[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=[O:14])[C:5]([Cl:9])=[CH:4][N:3]=1

参加物

6

反応物 4

HCID 227Anthranilic AcidHCID 62657Potassium Phosphate, TribasicHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 534009652,5-Dichloro-4-iodopyridine

生成物 1

HCID 575168952-[(2,5-Dichloro-4-pyridinyl)amino]benzoic acid収率 73%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
120 °C

実験手順

A mixture of 2,5-dichloro-4-iodopyridine (10 g, 36.5 mmol), 2-aminobenzoic acid (4.85 g, 35.4 mmol), DPEPhos [bis(2-diphenylphosphinophenyl)ether] (1.6 g, 2.97 mmol), palladium(II) acetate (160 mg, 0.713 mmol) and K3PO4 (20 g, 94 mmol) was degassed and heated at 120° C. (oil bath temp) for 20 h. After 20 h, LCMS showed there was 33% (relative to the desired product) starting material left. Added another 160 mg of Pd(OAc)2 to the mixture, and heated to 120° C. for another 24 h. LCMS showed conversion complete. The mixture was cooled to room temperature, followed by filtration, and washing with EtOAc. The solids were acidified to pH=7-8, followed by filtration. However, the mixture was a paste, and collected solids could not be dried completely. The solids (11 g) was acidified with 6N HCl to pH=1. The resulting paste was filtered, and washed with water and TBME. The solid was dried under vacuum over P2O5 for 2 days to give the title compound (7.32 g, 60.2% yield). MS: M(C12H8Cl2N2O2)=283.11, (M+H)+=283.8; 1H NMR (400 MHz, DMSO) ppm 13.6 (s, 1 H) 10.2 (s, 1 H) 8.3 (s, 1 H) 8.0 (d, 1 H) 7.6 (q, 2 H) 7.3 (s, 1 H) 7.2 (m, 1 H).

後処理

  1. customwas degassed
  2. waitleft
  3. additionAdded another 160 mg of Pd(OAc)2 to the mixture
  4. temperatureheated to 120° C. for another 24 h
  5. temperatureThe mixture was cooled to room temperature
  6. filtrationfollowed by filtration
  7. washwashing with EtOAc
  8. filtrationfollowed by filtration
  9. customcollected solids could not
  10. custombe dried completely
  11. filtrationThe resulting paste was filtered
  12. washwashed with water and TBME
  13. dry with materialThe solid was dried under vacuum over P2O5 for 2 days

出典と根拠

ORDレコード
ord-8811a674fced4e168604c445c868849b
出典データセット
uspto-grants-2015_04
特許番号
US09012479B2

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