Sodium Carbonate → HCID 59065920, compound

HRID 25743Notes

Reaction equation

HRID 25743 reaction equation
[Si:1]([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])[NH:24][C:23]2=[O:29])[O:11][CH:10]1[C@H:30]([OH:62])[C@@H:31]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[NH:32][CH2:33][CH2:34][CH2:35][NH:36][C:37](=[O:54])[C@H:38]([CH2:50][CH:51]([CH3:53])[CH3:52])[NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:63](OC(=O)N[C@@H](C(=O)NCCC=O)CC(C)C)[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1.[C:86](N[C@@H](C(O)=O)CC(C)C)(OCC1C=CC=CC=1)=[O:87].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C(O)(=O)C>[Si:1]([O:8][C@H:9]1[C@@H:13]([O:14][Si:15]([C:18]([CH3:19])([CH3:21])[CH3:20])([CH3:17])[CH3:16])[C@H:12]([N:22]2[CH:27]=[CH:26][C:25](=[O:28])[N:24]([CH2:63][C:64]3[CH:65]=[CH:66][C:67]([O:87][CH3:86])=[CH:68][CH:69]=3)[C:23]2=[O:29])[O:11][CH:10]1[C@H:30]([OH:62])[C@@H:31]([C:55]([O:57][C:58]([CH3:60])([CH3:59])[CH3:61])=[O:56])[NH:32][CH2:33][CH2:34][CH2:35][NH:36][C:37](=[O:54])[C@@H:38]([CH2:50][CH:51]([CH3:52])[CH3:53])[NH:39][C:40](=[O:49])[O:41][CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 7000099N-Cbz-D-leucineHCID 59065937HCID 59065937, compoundHCID 86587959[(1R)-3-methyl-1-(3-oxo-propylcarbamoyl)butyl]-carbamic acid benzyl ester

Product 1

HCID 59065920HCID 59065920, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(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 (62 mg, 0.086 mmol, obtained from Reference Example 6) and [(1R)-3-methyl-1-(3-oxo-propylcarbamoyl)butyl]-carbamic acid benzyl ester (33 mg, 0.103 mmol, obtained from N-CBZ-D-leucine in an similar manner described in Reference Example 15 and 16) in anhydrous tetrahydrofuran was stirred at room temperature under a nitrogen atmosphere for 15 minutes. Acetic acid (2 drops) and sodium triacetoxyborohydride (36 mg, 0.17 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 (3×50 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 (5R,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 (37 mg, 42%) as a white amorphous solid.

Workup

  1. stirringthe resulting solution was stirred under nitrogen for an additional 2.5 hours
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×50 ml)
  3. washThe combined extracts were washed with saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed (flash column, silica gel, 2.5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-63c2ee21c7524ffc9ef2d2ecedbbf78a
Source dataset
uspto-grants-2005_02
Patent number
US06858591B2

Reaction notes

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