Water → HCID 11441321, compound

HRID 1058543Notes

Reaction equation

HRID 1058543 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH2:11][C@H:10]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:9]([N:20]=[N+]=[N-])[C@H:8]([O:23][CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])[CH:7]=1)=[O:5])[CH3:2].O.C(N(CC)CC)C.[C:37](OC(=O)C)(=[O:39])[CH3:38].C(P(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH2:11][C@H:10]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:9]([NH:20][C:37](=[O:39])[CH3:38])[C@H:8]([O:23][CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])[CH:7]=1)=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 962WaterHCID 7918Acetic AnhydrideHCID 8471Triethylamine2×HCID 13831TributylphosphineHCID 11257980(3R,4R,5S)-4-azido-5-tert.-butoxycarbonylamino-3-(1-ethylpropoxy)cyclohex-1-enecarboxylic acid ethylester

Product 1

HCID 11441321HCID 11441321, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1.59 g (3R,4R,5S)-4-azido-5-tert.-butoxycarbonylamino-3-(1-ethyl-propoxy)-cyclohex-1-enecarboxylic acid ethyl ester (4 mmol) and 0.36 ml water (20 mmol) in 5 ml tetrahydrofuran was cooled to 0° C. 1.12 ml triethylamine (8 mmol) and 0.38 ml acetic anhydride were added and stirring at 0° C. was continued for 15 min. 1.14 ml tri-n-butyl phosphine (4.4 mmol) were added over 5 min. and the yellowish solution was stirred for 30 min. at 0° C. and then for 1 h at room temperature. After the addition of 5.58 ml triethylamine (40 mmol) 1.89 ml acetic anhydride (20 mmol) were added slowly under ice cooling and stirring at room temperature was continued for 1 h. The reaction mixture was diluted with 30 ml ethyl acetate and washed sequentially with 25 ml 2N HCl, 10 ml 10% Na2CO3 and 20 ml 10% brine. The aqueous layers were extracted sequentially with 20 ml ethyl acetate. The combined organic layers were dried (Na2SO4) and the solvent was removed by rotary evaporation (30° C./210 mbar) affording 2.89 g crude, which was purified by chromatography on SiO2 (100 g) with hexane ethyl acetate 1.4:1 (100 ml fractions). Rotary evaporation (30° C./≧10 mbar) gave 1.39 g (84%) of the title product as a colorless, crystalline residue, m.p. 153.5-154.5° C. [α]D=−89.7° (CHCl3; c=1)

Workup

  1. stirringthe yellowish solution was stirred for 30 min. at 0° C.
  2. waitfor 1 h at room temperature
  3. additionwere added slowly under ice cooling
  4. stirringstirring at room temperature
  5. waitwas continued for 1 h
  6. washwashed sequentially with 25 ml 2N HCl, 10 ml 10% Na2CO3 and 20 ml 10% brine
  7. extractionThe aqueous layers were extracted sequentially with 20 ml ethyl acetate
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. customthe solvent was removed by rotary evaporation (30° C./210 mbar)
  10. customaffording 2.89 g crude, which
  11. customwas purified by chromatography on SiO2 (100 g) with hexane ethyl acetate 1.4:1 (100 ml fractions)
  12. customRotary evaporation (30° C./≧10 mbar)

Sources & evidence

ORD record
ord-486ec5162efb4d8aaa5b160081ca9c4b
Source dataset
uspto-grants-2003_02
Patent number
US06518048B2

Reaction notes

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