Trifluoroacetic acid → (5S,12S)-12-[(R)-[(3R,4R,5R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-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-oic acid

HRID 25738Notes

Reaction equation

HRID 25738 reaction equation
[Si]([O:8][C@H:9]1[C@@H:13]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C@H:12]([N:22]2[CH:27]=[CH:26][C:25](=[O:28])[N:24]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[C:23]2=[O:38])[O:11][CH:10]1[C@H:39]([OH:70])[C@@H:40]([C:63]([O:65]C(C)(C)C)=[O:64])[NH:41][CH2:42][CH2:43][CH2:44][NH:45][C:46](=[O:62])[C@H:47]([C@@H:59]([OH:61])[CH3:60])[NH:48][C:49](=[O:58])[O:50][CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O>FC(F)(F)C(O)=O.C(Cl)Cl>[Si:15]([O:14][C@H:13]1[C@H:12]([N:22]2[CH:27]=[CH:26][C:25](=[O:28])[N:24]([CH2:29][C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)[C:23]2=[O:38])[O:11][CH:10]([C@H:39]([OH:70])[C@@H:40]([C:63]([OH:65])=[O:64])[NH:41][CH2:42][CH2:43][CH2:44][NH:45][C:46](=[O:62])[C@H:47]([C@@H:59]([OH:61])[CH3:60])[NH:48][C:49](=[O:58])[O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C@H:9]1[OH:8])([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:16])[CH3:17]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86587943tert-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-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate

Product 1

HCID 69752535(5S,12S)-12-[(R)-[(3R,4R,5R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-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-oic acidYield 95%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of trifluoroacetic acid (0.3 drops) in methylene chloride (1 ml) was cooled to 0° C. 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-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate (20 mg, 0.02 mmol, obtained from Example 10) was added and the resulting mixture was stirred at 0° C. for 20 minutes. Additional trifluoroacetic acid (0.9 ml) was gradually added over 1 hour after which the mixture was warmed to room temperature and stirred for 2 hours. The volatiles were removed in vacuo. The residue was azeotroped with toluene, and was then dissolved in methylene chloride (0.5 ml). Cold trifluoroacetic acid (0.5 ml) and the mixture was stirred for 3 hours. The volatiles were removed in vacuo and the residue was azeotroped with toluene to provide (5S,12S)-12-[(R)-[(3R,4R,5R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-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-oic acid (16 mg, 95%) as a yellow solid.

Workup

  1. additionwas added
  2. temperaturewas warmed to room temperature
  3. stirringstirred for 2 hours
  4. customThe volatiles were removed in vacuo
  5. customThe residue was azeotroped with toluene
  6. dissolutionwas then dissolved in methylene chloride (0.5 ml)
  7. stirringCold trifluoroacetic acid (0.5 ml) and the mixture was stirred for 3 hours
  8. customThe volatiles were removed in vacuo
  9. customthe residue was azeotroped with toluene

Sources & evidence

ORD record
ord-818d21f1b9bb4902b537422aec04034e
Source dataset
uspto-grants-2005_02
Patent number
US06858591B2

Reaction notes

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