Isopropyl Acetate → Acoziborole

HRID 60554

反応式

HRID 60554 の反応式
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([CH3:11])([CH3:10])[O:8][B:7]([OH:12])[C:6]=2[CH:13]=1.C([O-])([O-])=O.[K+].[K+].[F:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[C:23]([C:30]([F:33])([F:32])[F:31])[CH:22]=1.C(OC(C)C)(=O)C>O.CC(C)=O.C1COCC1>[F:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[C:9]([CH3:10])([CH3:11])[O:8][B:7]([OH:12])[C:6]=3[CH:13]=2)=[O:26])=[C:23]([C:30]([F:31])([F:32])[F:33])[CH:22]=1

参加物

8

反応物 4

HCID 7915Isopropyl AcetateHCID 11430Potassium CarbonateHCID 6056804-Fluoro-2-(trifluoromethyl)benzoyl chlorideHCID 583731006-amino-3,3-dimethylbenzo[c][1,2]oxaborol-1(3H)-ol2 回

生成物 1

HCID 44178354Acoziborole収率 113.1%

試薬・触媒・溶媒 3

HCID 180Acetone溶媒HCID 962Water溶媒3 回HCID 8028Tetrahydrofuran溶媒

実験手順

A 22 L four-necked round-bottomed-flask equipped with a nitrogen inlet adapter, mechanical stirrer and thermocouple was charged with 6-amino-3,3-dimethyl-3H-benzo[c][1,2]oxaborol-1-ol (554 g, 3.13 mol), THF (5.5 L, anhydrous, stabilizer free) and K2CO3 (865 g, 6.26 mol). The suspension was stirred at room temperature for 30 min and 4-fluoro-2-(trifluoromethyl)benzoyl chloride (780 g, 3.44 mol) was added over 30 min. The resulting suspension was aged for 24 h at room temperature. HPLC showed unreacted 6-amino-3,3-dimethyl-3H-benzo[c][1,2]oxaborol-1-ol so an additional 42 mL of the acid chloride was added. After 30 min, water (2.8 L) and isopropyl acetate (5.5 L) were added and the phases were partitioned. The organic phase was further extracted with water (2.8 L) and then brine (2.8 L). The organic phase was dried over MgSO4 and concentrated in vacuo to provide a tan solid. The solid was dissolved with acetone (3.0 L) and transferred to a mechanically stirred 50 L round-bottomed-flask. Distilled water (2.0 L) was added in one portion and the mixture was stirred for 30 min to produce a seed bed and then additional water (1.0 L) was added over 30 min. The suspension was stirred at room temperature overnight and the solids were collected on a frit. The cake was rinsed with 1:1 acetone/water (1.0 L) and air dried to constant weight to provide 4-fluoro-N-(1-hydroxy-3,3-dimethyl-1,3-dihydro-benzo[c][1,2]oxaborol-6-yl)-2-trifluoromethyl benzamide as a dark tan solid (1.3 kg).

後処理

  1. customA 22 L four-necked round-bottomed-flask equipped with a nitrogen inlet adapter, mechanical stirrer
  2. waitThe resulting suspension was aged for 24 h at room temperature
  3. additionwas added
  4. waitAfter 30 min
  5. customthe phases were partitioned
  6. extractionThe organic phase was further extracted with water (2.8 L)
  7. dry with materialThe organic phase was dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customto provide a tan solid
  10. stirringthe mixture was stirred for 30 min
  11. customto produce a seed bed
  12. stirringThe suspension was stirred at room temperature overnight
  13. customthe solids were collected on a frit
  14. washThe cake was rinsed with 1:1 acetone/water (1.0 L) and air
  15. customdried to constant weight

出典と根拠

ORDレコード
ord-2aadae9e143b4c0eb602a07705c367bb
出典データセット
uspto-grants-2016_09
特許番号
US09440994B2

関連ノート

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