Triethylamine → HCID 67278263, 화합물

HRID 1694402노트

반응식

HRID 1694402 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

HCID 67278263HCID 67278263, 화합물수율 68%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0c47d12b129941b4b4a9e45d92196bc5
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158673B2

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