Sodium Carbonate → HCID 59065910, compound

HRID 25708Notes

Reaction equation

HRID 25708 reaction equation
[CH2:1]([O:8][C:9](=[O:24])[NH:10][CH:11]([C:17](=[O:23])[NH:18][CH2:19][CH2:20][CH:21]=O)[CH:12]([OH:16])[CH:13]([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:25][C@@H:26]([C@H:34]([C@@H:36]1[C@@H:40]([O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[C@@H:39]([O:49][Si:50]([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51])[C@H:38]([N:57]2[CH:62]=[CH:61][C:60](=[O:63])[N:59]([CH2:64][C:65]3[CH:70]=[CH:69][C:68]([O:71][CH3:72])=[CH:67][CH:66]=3)[C:58]2=[O:73])[O:37]1)[OH:35])[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C(O)(=O)C>[Si:42]([O:41][C@H:40]1[C@@H:39]([O:49][Si:50]([C:53]([CH3:55])([CH3:56])[CH3:54])([CH3:51])[CH3:52])[C@H:38]([N:57]2[CH:62]=[CH:61][C:60](=[O:63])[N:59]([CH2:64][C:65]3[CH:70]=[CH:69][C:68]([O:71][CH3:72])=[CH:67][CH:66]=3)[C:58]2=[O:73])[O:37][CH:36]1[C@H:34]([OH:35])[C@@H:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[NH:25][CH2:21][CH2:20][CH2:19][NH:18][C:17](=[O:23])[C@H:11]([C@@H:12]([OH:16])[CH:13]([CH3:15])[CH3:14])[NH:10][C:9](=[O:24])[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([C:45]([CH3:46])([CH3:47])[CH3:48])([CH3:44])[CH3:43]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12137063tert-butyl (2S,3R)-2-amino-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-3-hydroxy-propanoateHCID 20759880[2-Hydroxy-3-methyl-1-(3-oxo-propylcarbamoyl)-butyl]-carbamic acid benzyl ester

Product 1

HCID 59065910HCID 59065910, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of [2-hydroxy-3-methyl-1-(3-oxo-propylcarbamoyl)-butyl]-carbamic acid benzyl ester (175 mg, 0.519 mmol, obtained from Reference Example 14) and tert-butyl (2S,3R)-2-amino-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl-(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-3-hydroxypropanoate (300 mg, 0.416 mmol, obtained from Reference Example 6) in anhydrous tetrahydrofuran was stirred at room temperature under a nitrogen atmosphere for 15 minutes. Acetic acid (3 drops) and sodium triacetoxyborohydride (176 mg, 0.831 mmol) were added and the resulting solution was stirred under nitrogen for an additional 2.5 hours. The reaction mixture was basified to pH 9 with aqueous sodium carbonate solution, and the aqueous layer was extracted with ethyl acetate (3×75 mL). The combined extracts were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed (flash column, silica gel, 2.5% methanol in methylene chloride) to provide tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxy-2-methylpropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (258 mg, 60%) as a white amorphous solid.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate (3×75 mL)
  2. washThe combined extracts were washed with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed (flash column, silica gel, 2.5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-48641ab90953477486fe92eb7164390e
Source dataset
uspto-grants-2005_02
Patent number
US06858591B2

Reaction notes

Loading…