4-Methylmorpholine → HCID 131712766, compound

HRID 1759002Notes

Reaction equation

HRID 1759002 reaction equation
CN1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[C:8]([O:12][C:13]([NH:15][C:16]1(OC=C[CH2:22]1)[CH2:17]CC(O)=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].C([O:28]C(Cl)=O)C.[CH3:32][C:33]([O:35][CH2:36][C:37]1[CH2:46][S:45][C@@H:40]2[C@H:41]([NH2:44])[C:42](=[O:43])[N:39]2[C:38]=1[C:47]([OH:49])=[O:48])=[O:34]>C1COCC1.C(N(CC)CC)C>[C:8]([O:12][C:13]([NH:15][CH:16]([CH2:17][C:6]1[O:5][CH:4]=[CH:3][CH:7]=1)[C:22]([NH:44][CH:41]1[C:42](=[O:43])[N:39]2[C:38]([C:47]([OH:49])=[O:48])=[C:37]([CH2:36][O:35][C:33](=[O:34])[CH3:32])[CH2:46][S:45][C@H:40]12)=[O:28])=[O:14])([CH3:9])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4413287-Aminocephalosporanic acidHCID 70549385HCID 70549385, compound

Product 1

HCID 131712766HCID 131712766, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 8471TriethylamineSolvent

Procedure

1.7 pts. by wt. of triethylamine and 0.1 pt. by wt. of N-methylmorpholine are added to a solution of 3.7 pts. by wt. of 2-t-butoxycarbonylamino-furfurylacetic acid in 60 pts. by vol. of abs. THF. The mixture is cooled to -25°, a solution of 1.8 pts. by wt. of chloroformic acid ethyl ester in 10 pts. by vol. of abs. THF is added and the mixture is stirred at this temperature for 15 minutes. A solution, pre-cooled to -20°, of silylated 7-aminocephalosporanic acid (7-ACS) in 40 pts. by vol. of abs. THF (prepared from 5.0 pts. by wt. of 7-ACS and 5.6 pts. by wt. of bis-trimethylsilylacetamide) is then added and the mixture is stirred for 10 minutes at -20° and allowed to come to room temperature. 80 pts. by vol. of ice-water are added, the mixture is adjusted to pH 7.3 and the THF is stripped off. The aqueous phase is extracted with ethyl acetate and is acidified at 0°-5° and again extracted with ethyl acetate. The latter ethyl acetate extracts are dried over magnesium sulphate and concentrated. The product (7.5 pts. by wt.) is obtained as a yellow foam, which can be further processed directly.

Workup

  1. temperatureThe mixture is cooled to -25°
  2. stirringthe mixture is stirred for 10 minutes at -20°
  3. customto come to room temperature
  4. extractionThe aqueous phase is extracted with ethyl acetate
  5. customis acidified at 0°-5°
  6. extractionagain extracted with ethyl acetate
  7. dry with materialThe latter ethyl acetate extracts are dried over magnesium sulphate
  8. concentrationconcentrated
  9. customThe product (7.5 pts. by wt.) is obtained as a yellow foam, which

Sources & evidence

ORD record
ord-ff67ed1980e94907bebd0d23817c977c
Source dataset
uspto-grants-1982_07
Patent number
US04338434

Reaction notes

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