Di-tert-butyl dicarbonate → HCID 86603398, compound

HRID 32840Notes

Reaction equation

HRID 32840 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:47])[C@@H:12]([NH:21][C:22](=[O:46])[C@H:23]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C:24]2[CH:29]=[CH:28][C:27]([NH:30]C(OC(C)(C)C)=O)=[CH:26][CH:25]=2)[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[S:8][CH:9]=1)=[O:4].C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C>FC(F)(F)C(O)=O.ClCCl.O1CCCC1>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:47])[C@@H:12]([NH:21][C:22](=[O:46])[C@@H:23]([C:24]2[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=2)[NH:38][C:39]([O:41][C:42]([CH3:44])([CH3:45])[CH3:43])=[O:40])[C@H:13]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:14])[S:8][CH:9]=1)=[O:4]

Participants

6

Reactant 2

HCID 90495Di-tert-butyl dicarbonateHCID 866033972-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester

Product 1

HCID 86603398HCID 86603398, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-{(2S,3S)-2-[(R)-2-tert-butoxycarbonylamino-2-(4-tert-butoxycarbonylamino-phenyl)-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester (510 mg, 0.76 mmol) was dissolved in 30% v/v trifluoroacetic acid in dichloromethane solution (10 mL) at 0° C. The mixture was stirred at 0° C. for 2.5 hours and then partitioned between ethyl acetate and saturated aqueous sodium carbonate. The aqueous layer was adjusted to pH=9 by the addition of solid sodium carbonate and the organic layer collected, dried over sodium sulfate, filtered and concentrated. The residue was without further purification dissolved in tetrahydrofuran (50 mL) and the resulting solution cooled to 0° C. A solution of di-tert-butyldicarbonate (167 mg, 0.76 mmol) in tetrahydrofuran (5 mL) was added dropwise and after stirring overnight the reaction mixture was evaporated and the residue was purified by chromatography over silica gel gradient eluted with 0 to 100% ethyl acetate in hexanes to afford 2-{(2S,3S)-2-[(R)-2-(4-amino-phenyl)-2-tert-butoxycarbonylamino-acetylamino]-3-phenyl-butyrylamino}-thiazole-4-carboxylic acid methyl ester as a white solid (250 mg, 58%).

Workup

  1. custompartitioned between ethyl acetate and saturated aqueous sodium carbonate
  2. additionThe aqueous layer was adjusted to pH=9 by the addition of solid sodium carbonate
  3. customthe organic layer collected
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was without further purification
  8. dissolutiondissolved in tetrahydrofuran (50 mL)
  9. temperaturethe resulting solution cooled to 0° C
  10. stirringafter stirring overnight the reaction mixture
  11. customwas evaporated
  12. customthe residue was purified by chromatography over silica gel gradient
  13. washeluted with 0 to 100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-feb64ebd7cb2485c8ff5a6e44cd16da0
Source dataset
uspto-grants-2008_09
Patent number
US07427635B2

Reaction notes

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