Methane → 4'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide

HRID 51965

反応式

HRID 51965 の反応式
[NH2:1][C:2]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)=O.CC(C)=O.[F:18][C:19]([F:36])([F:35])[C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:27]([C:32](Cl)=[O:33])=[CH:28][CH:29]=[CH:30][CH:31]=2)=[CH:22][CH:21]=1.O=[Si]=O.C(NCC)C.C>C1COCC1.C(Cl)Cl>[NH2:1][C:2]1[CH:9]=[C:8]([NH:10][C:32]([C:27]2[C:26]([C:23]3[CH:24]=[CH:25][C:20]([C:19]([F:18])([F:35])[F:36])=[CH:21][CH:22]=3)=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:33])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]

参加物

9

反応物 6

HCID 297MethaneHCID 8021DiethylamineHCID 24261SilicaHCID 110660004'-(Trifluoromethyl)-[1,1'-biphenyl]-2-carbonyl chlorideHCID 111477482,4-DiaminobenzaldehydeHCID 18522661Acetone cardice

生成物 1

HCID 101346044'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide収率 30%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a nitrogen purged 12 liter 3-neck flask fitted with a mechanical stirrer and temperature probe was added THF (4.3 L) and 2,4-diaminobenzaldehyde (50 g, 0.37 mol, 1 equiv). After cooling the solution to −70° C. (dry ice/acetone bath), poly(4-vinylpyridine), which can be obtained from Aldrich, Milwaukee, Wis., 25% cross-linked, (210 g) was added. A solution of 4′-trifluoromethyl-biphenyl-2-carbonyl chloride (105 g, 0.37 mol, 1 equiv) in THF (1 L) was added at such a rate as to maintain the temperature below −60° C. The light orange reaction mixture was allowed to warm to room temperature over 4 hours to give a dark red reaction mixture. (HPLC analysis showed an 18:1 mixture of mono- (retention time (rt)=4.8 min) to di- (rt=3.1 min) acylated products along with 5% residual starting material (rt=18.8 min), (Zorbax SIL (150 mm) from Agilent Technologies, Palo Alto, Calif. 2 mL/min 90:10 hexanes/isopropanol, 0.1% diethylamine, 250 nm, 40° C.). The reaction was quenched with 1 N NaOH (450 mL) and allowed to stir overnight at 25° C. The reaction mixture was filtered and the solids were washed with ethyl acetate (5×200 mL) and the combined organic layers were concentrated in vacuo to give a brown oil. The oil was dissolved in CH2Cl2 (1.5 L) and silica gel (EM Science, Gibbstown, N.J., 230-400 mesh or 0.04-0.06 mm particle size) (410 g) and Darco G-60® (10 g, BNL Fine Chemicals and Reagents) were added. The slurry was stirred for 15 minutes and filtered. The silica was washed with CH2Cl2 (5×200 mL). The combined organic layers were concentrated in vacuo and the methylene chloride was displaced with 1:1 hexanes/diisopropylether. The precipitated product was collected by suction filtration and dried in air to give 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-4-formyl-phenyl)-amide (40 g, 30%, 43:1 mono:bis acylated by HPLC) as a light yellow solid.

後処理

  1. customTo a nitrogen purged 12 liter 3-neck flask
  2. customfitted with a mechanical stirrer
  3. addition, 25% cross-linked, (210 g) was added
  4. temperatureto maintain the temperature below −60° C
  5. customto give
  6. customa dark red reaction mixture
  7. additionan 18:1 mixture of mono- (retention time (rt)=4.8 min) to di- (rt=3.1 min)
  8. customThe reaction was quenched with 1 N NaOH (450 mL)
  9. filtrationThe reaction mixture was filtered
  10. washthe solids were washed with ethyl acetate (5×200 mL)
  11. concentrationthe combined organic layers were concentrated in vacuo
  12. customto give a brown oil
  13. stirringThe slurry was stirred for 15 minutes
  14. filtrationfiltered
  15. washThe silica was washed with CH2Cl2 (5×200 mL)
  16. concentrationThe combined organic layers were concentrated in vacuo
  17. filtrationThe precipitated product was collected by suction filtration
  18. customdried in air

出典と根拠

ORDレコード
ord-29bed8aeea5c493dafdce644dfd17e00
出典データセット
uspto-grants-2004_03
特許番号
US06713489B2

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