Triethylamine → HCID 67278263、化合物

HRID 1694402ノート

反応式

HRID 1694402 の反応式
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([Cl:12])[CH:3]=1.[CH2:13]([N:15](CC)[CH2:16][CH3:17])[CH3:14].N1CCCC1.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>CCOC(C)=O>[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([N:15]2[CH2:16][CH2:17][CH2:14][CH2:13]2)=[O:8])=[C:4]([Cl:12])[CH:3]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 31268PyrrolidineHCID 111923Propylphosphonic anhydrideHCID 27362254-Bromo-2-chloro-5-fluorobenzoic acid

生成物 1

HCID 67278263HCID 67278263、化合物収率 68%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a stirring solution of 4-bromo-2-chloro-5-fluorobenzoic acid (50 g, 0.25 mol) in 200 mL of EtOAc at 0° C. (ice/water bath) was added triethyl amine (237 mL, 0.50 mol), pyrrolidine (41.2 mL, 0.5 mol), followed by 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (CAS # 68957-94-8) (237 mL, 0.37 mol, 50 wt %, EtOAc). After 1 hr, the reaction was quenched with a saturated solution of NaHCO3, and extracted with EtOAc, and CH2Cl2. The combined organic layers were dried over MgSO4, filtered and concentrated. Purification of this material was accomplished by flash column chromatography using a Biotage™ 75L column, eluting with a gradient of 2%-50% EtOAc/hexanes. The product containing fractions were collected and concentrated to give the title compound (52 g, 68% yield) as a white solid: Rf=0.23 (40% EtOAc/hexanes): LRMS m/z Calcd for C11H10BrClFNO, 306.6, found, 306, 308, 310 (M+1) APCI; 1H NMR (300 MHz, CDCl3): δ 7.53 (d, J=6.2 Hz, 1H), 7.02 (d J=7.9 Hz, 1H), 3.54 (apt t, J=6.6 Hz, 2H), 3.13 (apt t, J=6.6 Hz, 2H), 1.92-1.83 (m, 4H); 100 MHz 13C NMR (CDCl3) δ 164.5, 158.1 (d, JC-F=249.5 Hz), 138.2, 134.3, 126.0, 115.5 (d, JC-F=25.5 Hz), 110.3 (d, JC-F=22.5 Hz), 47.0, 45.8, 26.0, 24.6.

後処理

  1. customthe reaction was quenched with a saturated solution of NaHCO3
  2. extractionextracted with EtOAc, and CH2Cl2
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of this material
  7. washeluting with a gradient of 2%-50% EtOAc/hexanes
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrated

出典と根拠

ORDレコード
ord-0c47d12b129941b4b4a9e45d92196bc5
出典データセット
uspto-grants-2012_04
特許番号
US08158673B2

反応ノート

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