Hydrochloric Acid → Methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]-3-hydroxypropanoate

HRID 1930190ノート

反応式

HRID 1930190 の反応式
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]([O:25][CH3:26])=[O:24])=[CH:18][C:17]=3[Cl:27])=[C:12]([F:28])[CH:11]=2)[C:7]([CH3:29])=[N:6][C:5]=1[CH3:30])(=[O:3])[NH2:2].[C:31](=O)([O-])[O-:32].[K+].[K+].C=O.Cl>CN(C=O)C.C(OCC)(=O)C.O>[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH:22]([CH2:31][OH:32])[C:23]([O:25][CH3:26])=[O:24])=[CH:18][C:17]=3[Cl:27])=[C:12]([F:28])[CH:11]=2)[C:7]([CH3:29])=[N:6][C:5]=1[CH3:30])(=[O:3])[NH2:2]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 11430Potassium CarbonateHCID 59627722Methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]acetate2 回

生成物 1

HCID 59627634Methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]-3-hydroxypropanoate収率 74%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
30 °C

実験手順

A stirred solution of methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-2′-fluorobiphenyl-4-yl)acetate (Intermediate 31-7; 615 g, 1437 mmol) in DMF (2.5 L) was cooled to 15° C., under a nitrogen atmosphere. Potassium carbonate (214 g, 1545 mmol) was then added followed by paraformaldehyde (47.5 g, 1581 mmol). The reaction was stirred for 5 hours at 30° C. The reaction was then added to stirred water (25.0 L) and ethyl acetate (10.0 L). Concentrated hydrochloric acid (430 ml) was then added slowly with stirring. The aqueous layer was separated and extracted with ethyl acetate (7.5 L). The organics were combined and washed with, 50% brine/water (10.0 L), dried (magnesium sulphate), filtered and the solvent was removed in vacuo. Gave methyl 2-[4-[4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-fluorophenyl]-3-chlorophenyl]-3-hydroxypropanoate (762 g) as a yellow gum, 64% by LCMS (therefore 488 g, 74% yield). The material was used crude in the next stage.

後処理

  1. additionThe reaction was then added
  2. stirringwith stirring
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (7.5 L)
  5. washwashed with, 50% brine/water (10.0 L)
  6. dry with materialdried (magnesium sulphate)
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo

出典と根拠

ORDレコード
ord-14b0f2d32d354d9dbd33af922163aaec
出典データセット
uspto-grants-2012_05
特許番号
US08188092B2

反応ノート

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