Acetic Anhydride → Ethyl 3-(acetyloxy)-6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

HRID 18009

반응식

HRID 18009 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:11][CH:10]=[C:9]([O:21][CH3:22])[C:8]=2[C:7]1=[O:23].OO.NC(N)=O.P([O-])([O-])(O)=O.[K+].[K+].S(=O)(O)[O-].[Na+].[C:46]([O:49]C(=O)C)(=[O:48])[CH3:47]>ClCCl.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C1(C)C=CC=CC=1>[C:46]([O:49][C:10]1[N:11]=[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:13]2[CH2:14][CH2:15][N:6]([CH2:5][C:4]3[CH:24]=[CH:25][C:26]([F:27])=[C:2]([Cl:1])[CH:3]=3)[C:7](=[O:23])[C:8]=2[C:9]=1[O:21][CH3:22])(=[O:48])[CH3:47]

참가 물질

9

반응물 5

HCID 7918Acetic AnhydrideHCID 24450Potassium Phosphate, DibasicHCID 31294Carbamide PeroxideHCID 23665763Sodium BisulfiteHCID 59455605Ethyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

생성물 1

HCID 59455606Ethyl 3-(acetyloxy)-6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

시약·촉매·용매 3

HCID 1140Toluene용매HCID 6344Dichloromethane용매HCID 9845Trifluoroacetic anhydride용매

반응 조건

온도
20 °C

실험 절차

To a cold (5° C.) mixture of ethyl 6-(3-chloro-4-fluorobenzyl)-4-methoxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (199 g, 0.51 mol) and urea hydrogen peroxide (100 g, 1.06 mol) in dichloromethane (1.5 L), trifluoroacetic anhydride was added dropwise over a period of 45 minutes. The resultant homogeneous solution was stirred at 20° C. for 30 minutes and cooled back to 5° C. The reaction mixture was treated with aqueous potassium hydrogen phosphate (pH of aqueous extract increased to ˜8), followed by slow addition of freshly prepared aqueous sodium bisulfite solution with the temperature of the product mixture maintained below 25° C. The organic extract was separated and the aqueous fraction extracted with toluene (2×). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Without further purification, a solution of this intermediate N-oxide (˜280 g) and acetic anhydride (239 mL, 2.5 mol) in toluene (2 L) was heated at 110° C. for 16 hours. The product mixture was concentrated under vacuum. The resultant oil was concentrated from toluene (300 mL, twice) and stored under vacuum overnight. The acetate product was used in the following step without further purification.

후처리

  1. additionwas added dropwise over a period of 45 minutes
  2. temperaturecooled back to 5° C
  3. temperaturemaintained below 25° C
  4. extractionThe organic extract
  5. customwas separated
  6. extractionthe aqueous fraction extracted with toluene (2×)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customWithout further purification
  11. concentrationThe product mixture was concentrated under vacuum
  12. concentrationThe resultant oil was concentrated from toluene (300 mL
  13. customstored under vacuum overnight
  14. customThe acetate product was used in the following step without further purification

출처 및 근거

ORD 기록
ord-24675255afd245cc91c2a4368071526f
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741315B2

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