Sodium Carbonate → 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-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

HRID 25710

Reaction equation

HRID 25710 reaction equation
[NH2:1][C@@H:2]([C@H:10]([C@@H:12]1[C@@H:16]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[C@@H:15]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[C@H:14]([N:33]2[CH:38]=[CH:37][C:36](=[O:39])[N:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=3)[C:34]2=[O:49])[O:13]1)[OH:11])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[CH2:50]([O:57][C:58](=[O:72])[NH:59][C@H:60]([C:65](=[O:71])[NH:66][CH2:67][CH2:68][CH:69]=O)[CH2:61][CH:62]([CH3:64])[CH3:63])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C(O)(=O)C>[Si:18]([O:17][C@H:16]1[C@@H:15]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:27])[CH3:28])[C@H:14]([N:33]2[CH:38]=[CH:37][C:36](=[O:39])[N:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[CH:43][CH:42]=3)[C:34]2=[O:49])[O:13][CH:12]1[C@H:10]([OH:11])[C@@H:2]([C:3]([O:5][C:6]([CH3:7])([CH3:9])[CH3:8])=[O:4])[NH:1][CH2:69][CH2:68][CH2:67][NH:66][C:65](=[O:71])[C@H:60]([CH2:61][CH:62]([CH3:64])[CH3:63])[NH:59][C:58](=[O:72])[O:57][CH2:50][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)([C:21]([CH3:22])([CH3:23])[CH3:24])([CH3:20])[CH3:19]

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 44366907[(1S)-3-methyl-1-(3-oxo-propylcarbamoyl)-butyl]-carbamic acid benzyl ester

Product 1

HCID 86587940tert-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-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oateYield 97.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 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-hydroxy-propanoate (200 mg, 0.277 mmol, obtained from Reference Example 6) and [(1S)-3-methyl-1-(3-oxo-propylcarbamoyl)-butyl]-carbamic acid benzyl ester (111 mg, 0.35 mmol, obtained from Reference Example 16) in anhydrous tetrahydrofuran (4 ml) was stirred at room temperature under a nitrogen atmosphere for 15 minutes. Acetic acid (4 drops) and sodium triacetoxyborohydride (117 mg, 0.55 mmol) were added, and the resulting solution was stirred under nitrogen for an additional 3.5 hours. The reaction mixture was basified to pH 9 with sodium carbonate aqueous solution, and the aqueous layer was extracted with ethyl acetate (3×80 ml). The combined extracts were washed with saturated sodium chloride, 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-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (276 mg, 97%), as a white amorphous solid.

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate (3×80 ml)
  2. washThe combined extracts were washed with saturated sodium chloride
  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-eed5a99c7d814845866f48db6f5f18e8
Source dataset
uspto-grants-2005_02
Patent number
US06858591B2

Linked notes

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