Sodium Bicarbonate → HCID 86632135, compound

HRID 889624Notes

Reaction equation

HRID 889624 reaction equation
[CH:1]([C@H:5]([C:14](=[O:94])[NH:15][C@@H:16]([CH2:90][CH:91]([CH3:93])[CH3:92])[C:17](=[O:89])[N:18]([CH3:88])[C@@H:19]([CH2:84][CH:85]([CH3:87])[CH3:86])[C:20](=[O:83])[NH:21][C@@H:22]([CH3:82])[C:23](=[O:81])[NH:24][C@H:25]([CH3:80])[C:26](=[O:79])[N:27]([CH3:78])[C@@H:28]([CH2:74][CH:75]([CH3:77])[CH3:76])[C:29](=[O:73])[NH:30][C@@H:31]([CH2:69][CH:70]([CH3:72])[CH3:71])[C:32](=[O:68])[N:33]([CH3:67])[C@@H:34]([CH:64]([CH3:66])[CH3:65])[C:35](=[O:63])[N:36]([CH3:62])[C@@H:37]([C@H:54]([OH:61])[C@H:55]([CH3:60])[CH2:56]/[CH:57]=[CH:58]/[CH3:59])[C:38](=[O:53])[NH:39][C@@H:40]([C@H:50]([OH:52])[CH3:51])[C:41](=[O:49])[N:42]([CH3:48])[CH2:43][C:44]([O:46]C)=[O:45])[NH:6]C(=O)OC(C)(C)C)([CH2:3][CH3:4])[CH3:2].C([O-])(O)=O.[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:6][C@H:5]([CH:1]([CH3:2])[CH2:3][CH3:4])[C:14](=[O:94])[NH:15][C@@H:16]([CH2:90][CH:91]([CH3:93])[CH3:92])[C:17](=[O:89])[N:18]([CH3:88])[C@@H:19]([CH2:84][CH:85]([CH3:87])[CH3:86])[C:20](=[O:83])[NH:21][C@@H:22]([CH3:82])[C:23](=[O:81])[NH:24][C@H:25]([CH3:80])[C:26](=[O:79])[N:27]([CH3:78])[C@@H:28]([CH2:74][CH:75]([CH3:76])[CH3:77])[C:29](=[O:73])[NH:30][C@@H:31]([CH2:69][CH:70]([CH3:71])[CH3:72])[C:32](=[O:68])[N:33]([CH3:67])[C@@H:34]([CH:64]([CH3:66])[CH3:65])[C:35](=[O:63])[N:36]([CH3:62])[C@@H:37]([C@H:54]([OH:61])[C@H:55]([CH3:60])[CH2:56]/[CH:57]=[CH:58]/[CH3:59])[C:38](=[O:53])[NH:39][C@@H:40]([C@H:50]([OH:52])[CH3:51])[C:41](=[O:49])[N:42]([CH3:48])[CH2:43][C:44]([OH:46])=[O:45]

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 86632136HCID 86632136, compound

Product 1

HCID 86632135HCID 86632135, compoundYield 61.5%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

Methyl (6R,9S,12S,15S,18R,21S,24S,27S,30S,33S)-6-sec-butyl-33-[(1R)-1-hydroxyethyl]-30-[(1R,2R,4E)-1-hydroxy-2-methyl-4-hexen-1-yl]-9,12,21,24-tetraisobutyl-27-isopropyl-2,2,11,15,18,20,26,29,35-nonamethyl-4,7,10,13,16,19,22,25,28,31,34-undecaoxo-3-oxa-5,8,11,14,17,20,23,26,29,32,35-undecaazaheptatriacontan-37-oate (80 mg) was dissolved in 20% TFA/CH2Cl2 (2 ml) under ice-bath cooling. After being stirred at the same temperature for 4 hrs, to the solution was added saturated NaHCO3 aqueous solution to be pH 8. The mixture was extracted with CHCl3 (20 ml) and the organic layer was washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated in vacuo. The resulting residue was dissolved in MeOH (4 ml). To the solution was added 1N LiOH (0.60 ml) under ice-bath cooling. After being stirred for 1 hr at the same temperature, the solution was acidified with 5% citric acid aqueous solution to be pH5, concentrated in vacuo to remove MeOH, and extracted with CHCl3 (20 ml). The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The resulting residue was triturated with Et2O to give (5S,8S,11S,14S,17S,20R,23S,26S,29S,32R)-32-amino-5-[(1R)-1-hydroxyethyl]-8-[(1R,2R,4E)-1-hydroxy-2-methyl-4-hexen-1-yl]-14,17,26,29-tetraisobutyl-11-isopropyl-3,9,12,18,20,23,27,33-octamethyl-4,7,10,13,16,19,22,25,28,31-decaoxo-3,6,9,12,15,18,21,24,27,30-decaazapentatriacontan-1-oic acid (45 mg) as a solid.

Workup

  1. temperaturecooling
  2. extractionThe mixture was extracted with CHCl3 (20 ml)
  3. washthe organic layer was washed with saturated NaHCO3 and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting residue was dissolved in MeOH (4 ml)
  7. additionTo the solution was added 1N LiOH (0.60 ml) under ice-bath
  8. temperaturecooling
  9. stirringAfter being stirred for 1 hr at the same temperature
  10. concentrationconcentrated in vacuo
  11. customto remove MeOH
  12. extractionextracted with CHCl3 (20 ml)
  13. washThe organic layer was washed with brine
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated in vacuo
  16. customThe resulting residue was triturated with Et2O

Sources & evidence

ORD record
ord-98ec4aa67f824440b90492726f15e7b8
Source dataset
uspto-grants-2012_08
Patent number
US08252895B2

Reaction notes

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