Phosphoric Acid → 1-(4-Chloro-phenyl)-7-hydroxy-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one

HRID 535323

反応式

HRID 535323 の反応式
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[CH:4][C:3]=1[O:11][CH3:12].P(=O)(O)(O)[OH:14].[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1>O>[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]2[C:6]3[C:5](=[CH:4][C:3]([O:11][CH3:12])=[C:2]([OH:1])[CH:7]=3)[CH2:8][C:9](=[O:14])[NH:10]2)=[CH:21][CH:20]=1

参加物

5

反応物 3

HCID 1004Phosphoric AcidHCID 77264-ChlorobenzaldehydeHCID 782204-Hydroxy-3-methoxyphenylacetonitrile

生成物 1

HCID 584382211-(4-Chloro-phenyl)-7-hydroxy-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one収率 58.7%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
120 °C

実験手順

To a suspension of 4-hydroxy-3-methoxyphenylacetonitrile (150 g, 0.919 mol) in phosphoric acid 85% (877 mL, 15.000 mol) was added 4-chlorobenzaldehyde (168 g, 1.195 mol), then the reaction mixture was heated at 120° C. for 2 h. After cooling to 90° C., the reaction mixture was slowly poured into the stirred 4 L of iced water. Resulting suspension was stirred at RT for 2 h, then filtered and washed with 500 ml of water 4 times. Crude and wet material was stirred in acetonitrile (1 L) at RT for 1 h, then filtration and dry up gave the title intermediate (163.6 g, 0.539 mol, 58.6%). HPLC: EtRet=4.20 min; LC-MS: m/z 304.0 [M+H]+; 1H-NMR (400 MHz, DMSO-d6): δ 3.25-3.53 (m, 2H), 3.72 (s, 3H), 5.47 (d, J=3.12 Hz, 1H), 6.53 (s, 1H), 6.72 (s, 1H), 7.24 (d, 2H), 7.37 (d, 2H), 8.42 (d, J=3.51 Hz, 1H), 8.86 (br. s., 1H).

後処理

  1. temperatureAfter cooling to 90° C.
  2. customResulting suspension
  3. filtrationfiltered
  4. washwashed with 500 ml of water 4 times
  5. stirringCrude and wet material was stirred in acetonitrile (1 L) at RT for 1 h
  6. filtrationfiltration
  7. customdry up

出典と根拠

ORDレコード
ord-97f99c1081f7440381ce51a829d053ca
出典データセット
uspto-grants-2014_10
特許番号
US08859535B2

関連ノート

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