Hydrochloric Acid → 2-(3-chloro-4,5-dihydro-1,2-oxazol-5-yl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic acid

HRID 127797Notes

Reaction equation

HRID 127797 reaction equation
[CH2:1]1[C:5]([Cl:6])=[N:4][O:3][C@@H:2]1[C@H:7]([NH2:11])[C:8]([OH:10])=[O:9].[C:12](=[O:15])(O)[O-:13].[Na+].O[CH2:18][CH:19]1[C:31]2[C:30](C(Cl)=O)=[CH:29][CH:28]=[CH:27][C:26]=2[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2.Cl>C(OCC)(=O)C.O>[Cl:6][C:5]1[CH2:1][CH:2]([CH:7]([NH:11][C:12]([O:13][CH2:18][CH:19]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[C:26]3[C:31]2=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:15])[C:8]([OH:10])=[O:9])[O:3][N:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 294641AcivicinHCID 516892Sodium BicarbonateHCID 86737604HCID 86737604, compound

Product 1

HCID 3323662-(3-chloro-4,5-dihydro-1,2-oxazol-5-yl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 178 mg. of AT-125 in 4 ml. of water is added 300 mg. of sodium bicarbonate. After cooling the mixture to 0°-5° C., 300 mg. of 9-hydroxymethyl fluorenylcarbonyl chloride is added and it is stirred for two hours and allowed to stand overnight at room temperature. The resulting semi solid is taken up in ethyl acetate and 1 N hydrochloric acid is added until a pH of 3 is attained. The organic phase is separated, dried over sodium sulfate, concentrated and chromatographed on 20 g. of CC-4 silica gel employing 40% ethyl acetate/Hexane. Those fractions containing the desired product are evaporated and the residue recrystallized from ethyl acetate to yield 3-chloro-α-[[(9H-fluoren-9-yl-methoxy)carbonyl]amino]-4,5-dihydro-5-isoxazole acetic acid, m.p. 182°-183° C. The NMR fits the desired structure.

Workup

  1. temperatureAfter cooling the mixture to 0°-5° C.
  2. waitto stand overnight at room temperature
  3. customThe organic phase is separated
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customchromatographed on 20 g
  7. additionThose fractions containing the desired product
  8. customare evaporated
  9. customthe residue recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-249339b08d544146bf777c88eeac94ea
Source dataset
uspto-grants-1981_03
Patent number
US04256898

Reaction notes

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