4-Methylmorpholine → Ampicillin

HRID 623328

반응식

HRID 623328 반응식
CN1CCOCC1.ClC(OCC(C)C)=O.[CH3:16][C:17]1([CH3:39])[S:21][C@@H:20]2[C@H:22]([NH:25][C:26]([C@H:28]([NH2:35])[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[O:27])[C:23](=[O:24])[N:19]2[C@H:18]1[C:36]([OH:38])=[O:37].O.O.O.CCN(CC)CC>C1COCC1.C1COCC1.O>[CH3:16][C:17]1([CH3:39])[S:21][C@@H:20]2[C@H:22]([NH:25][C:26]([C@H:28]([NH2:35])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:27])[C:23](=[O:24])[N:19]2[C@H:18]1[C:36]([OH:38])=[O:37]

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 23565Ampicillin TrihydrateHCID 62365Isobutyl chloroformate

생성물 1

HCID 6249Ampicillin수율 180.5%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 21881883Oxolane--water (1/1)용매

실험 절차

To a solution of acid 9 (22 mg, 0.023 mmol) and N-methyl morpholine (2.5 μL, 0.023 mmol) in 1 mL of anhydrous THF cooled to 0° C. was added isobutyl chloroformate (3.0 μL, 0.023 mmol) and the mixture was stirred for 1 hour at that temperature. A solution of ampicillin trihydrate (10.6 mg, 0.026 mmol) and Et3N (10 μL) in 1 mL of THF/H2O 4:1 was added and the mixture was stirred for 1 h at 0° C. and 1 h at room temperature. After removal of the THF under vacuum, the residue was dissolved in 5 mL of water and the solution was acidified to pH=2 with 1 N HCl. The resulting suspension was extracted with EtOAc (5 mL×3) and the combined organic layers were washed with brine, dried over Na2SO4 and filtered. The solvent was removed under vacuum and the residue was purified by preparative HPLC. The fractions containing product was combined and lyophilized to give conjugate 10 (16.4 mg, 55%) as a white solid: 1H NMR (600 MHz, DMSO-d6) δ9.06 (d, J=7.6 Hz, 1H), 8.54 (d, J=8.5 Hz, 1H), 8.31 (t, J=5.6 Hz, 3H), 7.40-7.44 (m, 5H), 7.24-7.36 (m, 9H), 7.12 (s, 1H), 5.71 (d, J=8.2 Hz, 1H), 5.46 (dd, J=7.9, 4.1 Hz, 1H), 5.35 (d, J=4.1 Hz, 1H), 4.11 (s, 1H), 3.12-3.16 (m, 6H), 2.43-2.45 (m, 2H), 2.30-2.34 (m, 2H), 2.27 (s, 9H), 2.20 (s, 9H), 1.59-1.65 (m, 6H), 1.53 (s, 3H), 1.37-1.43 (m, 9H); HRMS (ESI) calcd. for C63H72N7O21S (M+H)+: 1294.4496, found 1294.4522; HPLC retention time 5.57 min.

후처리

  1. stirringthe mixture was stirred for 1 h at 0° C. and 1 h at room temperature
  2. customAfter removal of the THF under vacuum
  3. dissolutionthe residue was dissolved in 5 mL of water
  4. extractionThe resulting suspension was extracted with EtOAc (5 mL×3)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customThe solvent was removed under vacuum
  9. customthe residue was purified by preparative HPLC
  10. additionThe fractions containing product

출처 및 근거

ORD 기록
ord-a3ee4e4b29b1461dba69cb5627613f35
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09302012B2

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