Sodium triacetoxyborohydride → tert-butyl (5S,12S)-12-[(S)-[(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-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

HRID 25714

Reaction equation

HRID 25714 reaction equation
[CH2:1]([O:8][C:9](=[O:22])[NH:10][C@H:11]([C:15](=[O:21])[NH:16][CH2:17][CH2:18][CH:19]=O)[C@@H:12]([OH:14])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:23][C@@H:24]([C@@H:32]([C@@H:34]1[C@@H:38]([O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[C@@H:37]([O:47][Si:48]([C:51]([CH3:54])([CH3:53])[CH3:52])([CH3:50])[CH3:49])[C@H:36]([N:55]2[CH:60]=[CH:59][C:58](=[O:61])[N:57]([CH2:62][C:63]3[CH:68]=[CH:67][C:66]([O:69][CH3:70])=[CH:65][CH:64]=3)[C:56]2=[O:71])[O:35]1)[OH:33])[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.O1CCCC1>[Si:40]([O:39][C@H:38]1[C@@H:37]([O:47][Si:48]([C:51]([CH3:53])([CH3:54])[CH3:52])([CH3:49])[CH3:50])[C@H:36]([N:55]2[CH:60]=[CH:59][C:58](=[O:61])[N:57]([CH2:62][C:63]3[CH:68]=[CH:67][C:66]([O:69][CH3:70])=[CH:65][CH:64]=3)[C:56]2=[O:71])[O:35][CH:34]1[C@@H:32]([OH:33])[C@@H:24]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[NH:23][CH2:19][CH2:18][CH2:17][NH:16][C:15](=[O:21])[C@H:11]([C@@H:12]([OH:14])[CH3:13])[NH:10][C:9](=[O:22])[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([C:43]([CH3:44])([CH3:45])[CH3:46])([CH3:42])[CH3:41]

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 59065916HCID 59065916, compoundHCID 86587933[(1S,2S)-2-hydroxy-1-(3-oxo-propylcarbamoyl)-propyl]-carbamic acid benzyl ester

Product 1

HCID 86587941tert-butyl (5S,12S)-12-[(S)-[(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-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oateYield 33.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

By using an analogous procedure to that described in Example 1, a solution of [(1S,2S)-2-hydroxy-1-(3-oxo-propylcarbamoyl)-propyl]-carbamic acid benzyl ester (99 mg, 0.32 mmol, obtained from Reference Example 18), tert-butyl (2S,3S)-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 (165 mg, 0.229 mmol, obtained from Reference example 5), acetic acid (4 drops) and sodium triacetoxyborohydride (97 mg, 0.457 mmol) in anhydrous tetrahydrofuran (4 ml) was stirred at room temperature under nitrogen for 4 hours. The residue was chromatographed (flash column, silica gel, 5% methanol in methylene chloride) to provide tert-butyl (5S,12S)-12-[(S)-[(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-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (77 mg, 33%) as a white amorphous solid.

Workup

  1. customThe residue was chromatographed (flash column, silica gel, 5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-6c6a445a373f40e1b123157e224cf170
Source dataset
uspto-grants-2005_02
Patent number
US06858591B2

Linked notes

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