Pyridine → HCID 90357861, compound

HRID 522188Notes

Reaction equation

HRID 522188 reaction equation
C([O:3][P:4]([CH2:9][C@@H:10]1[C@H:15]([NH:16][C:17](=[O:19])[CH3:18])[C@@H:14]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:13]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@@H:12]([CH2:36][O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:11]1)(=[O:8])[O:5]CC)C.N1C=CC=CC=1.C[Si](Br)(C)C>C(#N)C>[C:17]([NH:16][C@@H:15]1[C@@H:14]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@H:13]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@@H:12]([CH2:36][O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[O:11][C@@H:10]1[CH2:9][P:4](=[O:3])([OH:5])[OH:8])(=[O:19])[CH3:18]

Participants

5

Reactant 3

HCID 1049PyridineHCID 76113BromotrimethylsilaneHCID 10817736HCID 10817736, compound

Product 1

HCID 90357861HCID 90357861, compoundYield 123.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of diethyl(((2S,3R,4R,5S,6R)-3-acetamido-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)methyl)phosphonate (0.40 g, 0.64 mmol, 1.0 equiv) in dry acetonitrile (23.5 mL) was added pyridine (0.6 mL, 7.36 mmol, 11.5 equiv) at 0° C. under argon atmosphere. Then, anhydrous TMSBr (1.65 mL, 10.2 mmol, 16.0 equiv) dissolved in 16.5 mL of dry acetonitrile was added dropwise at −5 to 0° C. The resulting mixture was stirred for 10 minutes. The resulting reaction mixture was allowed to warm to room temperature 4 hours and then the volatiles were removed in vacuo (bath temperature <15° C.). To the residue was added ice-cold water (10 mL), and the organic material was extracted into DCM (2×10 mL). The organic layer was then dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo (bath temperature <15° C.) to obtain (((2S,3R,4R,5S,6R)-3-acetamido-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)tetrahydro-2H-pyran-2-yl)methyl)phosphonic acid (0.45 g) as a pale green solid. This material was directly taken forward to the next step without purification. ESI (M+1) 570.0; calc for C30H36NO8P 569.2.

Workup

  1. additionwas added dropwise at −5 to 0° C
  2. customThe resulting reaction mixture
  3. customthe volatiles were removed in vacuo (bath temperature <15° C.)
  4. additionTo the residue was added ice-cold water (10 mL)
  5. extractionthe organic material was extracted into DCM (2×10 mL)
  6. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo (bath temperature <15° C.)

Sources & evidence

ORD record
ord-03fcc1300c0245c797027f0a2d6bc26c
Source dataset
uspto-grants-2016_05
Patent number
US09328134B2

Reaction notes

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