Water → 71347-90-5

HRID 1416518Notes

Reaction equation

HRID 1416518 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][OH:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C@:15]12([CH2:25]S(O)(=O)=O)C(C)(C)[CH:19]([CH2:20][CH2:21]1)[CH2:18][C:16]2=O.[CH3:30][N:31](C)[CH:32]=[O:33].[C:35]([O-])(O)=O.[Na+].[OH2:40]>CC#N.O>[CH2:25]([O:40][C:32]([NH:31][CH2:30][CH2:35][O:14][CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])=[O:33])[C:15]1[CH:16]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 280458benzyl N-(2-hydroxyethyl)carbamateHCID 516892Sodium Bicarbonate

Product 1

HCID 309084971347-90-5

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of 3.5 grams (3.31 mmol) of 1-[4,5-dihydroxy-N2 -(4-octyloxybenzoyl)ornithine]-5-(3-hydroxyglutamine)-6-(3-hydroxyproline) echinocandin B, 16.13 grams (82.7 mmol) 2-(N-benzyloxycarbonylamino)ethanol and 768 milligrams (3.31 mmol) of (1S)-(+)-10-camphorsulfonic acid in 120 mL of anhydrous dixane and 12 mL of anhydrous N,N-dimethylformamide was stirred at 25° C. The reaction was monitored by analytical HPLC using "ZORBAX" RX-C18 column and a solvent system of 55% CH3CN/H2O at a flow rate of 1.5 mL/min with UV detection at 210 and 277 nm. After about 20 hours >95 percent conversion to product (tR =3.76 min) was noted. The reaction mixture was neutralized by the addition of 3.5 mL of 1M NaHCO3 and then diluted with 135 mL of H2O. The resulting solution was filtered and the filtrate pump-injected onto a "DELTA-PAK" C18 cartridge column (47 mm×30 cm) and eluted using step gradient (45-55% CH3CN/H2O) elution at a flow rate of 50 mL/min. The appropriate fractions were combined, diluted with 250 milliliters of water and the product recovered by solid-phase extraction using the same column in 5% CH3CN/H2O. The extracted material was pump-injected onto the column, then eluted with 95% CH3CN/H2O, the product containing eluates pooled, concentrated and lyophilized to obtain the N-benzyloxycarbonylaminoethyl ether intermediate in a yield of 2.3 grams (56%) as a white amorphous solid: HPLC assay at 210 nm >97% product. Mass spectrum: (FAB) 1242.7 (M+Li)+

Workup

  1. filtrationThe resulting solution was filtered
  2. washthe filtrate pump-injected onto a "DELTA-PAK" C18 cartridge column (47 mm×30 cm) and eluted
  3. washstep gradient (45-55% CH3CN/H2O) elution at a flow rate of 50 mL/min
  4. additiondiluted with 250 milliliters of water
  5. customthe product recovered by solid-phase extraction
  6. washeluted with 95% CH3CN/H2O
  7. additionthe product containing eluates
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-fd0a6eaaaf0a45ee99d175746451c496
Source dataset
uspto-grants-1999_06
Patent number
US05914313

Reaction notes

Loading…