Hydrochloric Acid → 5-Bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid

HRID 632336ノート

反応式

HRID 632336 の反応式
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([OH:11])=[O:10])=[N:6][C:7]=1Cl.[CH3:12][C:13]1([CH2:17][OH:18])[CH2:16][O:15][CH2:14]1.[H-].[Na+].Cl>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([OH:11])=[O:10])=[N:6][C:7]=1[O:18][CH2:17][C:13]1([CH3:12])[CH2:16][O:15][CH2:14]1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 1378373-Methyl-3-oxetanemethanolHCID 446077145-Bromo-6-chloropicolinic acid

生成物 1

HCID 710878905-Bromo-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid収率 27.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 5-bromo-6-chloropicolinic acid (Example 280a) (0.75 g, 3.17 mmol) in dry DMF (18 ml) under argon was added (3-methyloxetan-3-yl)-methanol (389 mg, 3.81 mmol) and NaH (279 mg, 6.98 mmol) was added by portions. The reaction mixture was stirred at room temperature for 20 min until gas release ceased. The reaction mixture was then stirred at 110° C. for 16 h. The reaction mixture was diluted with ethyl acetate, and the solution was poured into a separatory funnel with 10 ml aq. solution 1.0M HCl. After extraction, the organic phase was collected and the aqueous phase was back extracted with ethylacetate. The organic phases were combined, dried over Na2SO4 and evaporated down in vacuo. The residue was purified by preparative HPLC to give the title compound (260 mg, 27%), MS (EI): m/e=302.0 [M+H]+.

後処理

  1. additionwas added by portions
  2. stirringThe reaction mixture was then stirred at 110° C. for 16 h
  3. extractionAfter extraction
  4. customthe organic phase was collected
  5. extractionthe aqueous phase was back extracted with ethylacetate
  6. dry with materialdried over Na2SO4
  7. customevaporated down in vacuo
  8. customThe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-358fa2c0b8df4e219a58d39ae38ad124
出典データセット
uspto-grants-2016_04
特許番号
US09321727B2

反応ノート

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