Cerium(III) chloride → (2S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-5-hydroxy-4-(methoxymethyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 627149Notes

Reaction equation

HRID 627149 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]1[CH:15]=[C:14]([CH2:16][OH:17])[C:13](=[O:18])[CH2:12][N:11]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:26]N(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.F[B-](F)(F)F.C[O+](C)C.[Cl-].[Ce+3].[Cl-].[Cl-].[BH4-].[Na+]>C(Cl)Cl>[Si:1]([O:8][CH2:9][C@@H:10]1[CH:15]=[C:14]([CH2:16][O:17][CH3:26])[CH:13]([OH:18])[CH2:12][N:11]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 24636Cerium(III) chlorideHCID 88675Proton spongeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 4311764Sodium borohydrideHCID 89852514(S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-4-(hydroxymethyl)-5-oxo-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 89863076(2S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-5-hydroxy-4-(methoxymethyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 81.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of Intermediate 117 (7.3 g, 19.65 mmol) in DCM (180 mL) was added N1,N1,N8,N8-tetramethylnaphthalene-1,8-diamine (25.3 g, 117.89 mmol). Then it was cooled to 0° C. and trimethyloxonium tetrafluoroborate (8.72 g, 58.94 mmol) was added. The reaction was then stirred at rt for several hours until LCMS showed the starting material was all consumed. Then it was concentrated under reduced pressure. The residue was then taken up in 100 mL Et2O and filtered, washed with 100 mL Et2O. The organic layer was then washed with 10% citric acid, aq NaHCO3, brine, dried over MgSO4, filtered and concentrated. The residue was then taken up in MeOH (180 mL), cooled to 0° C. and cerium(III) chloride (7.32 g, 19.65 mmol) was then added to give a clear solution. Then NaBH4 (0.743 g, 19.65 mmol) was added as solid, and the mixture was stirred from 0° C. to rt for 1 hr. The reaction mixture was concentrated in vacuo. The white solid was redissolved in 200 mL Et2O and washed with 10% citric acid, NaHCO3, brine, dried over MgSO4, filtered and concentrated. The residue was purified by silica gel column (20-80% Hex/EA, 80 g) to afford the title compound (6.20 g, 81%) as a colorless oil (−3.8:1 mixture of 2 diastereomers).

Workup

  1. concentrationThen it was concentrated under reduced pressure
  2. filtrationfiltered
  3. washwashed with 100 mL Et2O
  4. washThe organic layer was then washed with 10% citric acid, aq NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. temperaturecooled to 0° C.
  9. customto give a clear solution
  10. stirringthe mixture was stirred from 0° C. to rt for 1 hr
  11. concentrationThe reaction mixture was concentrated in vacuo
  12. dissolutionThe white solid was redissolved in 200 mL Et2O
  13. washwashed with 10% citric acid, NaHCO3, brine
  14. dry with materialdried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe residue was purified by silica gel column (20-80% Hex/EA, 80 g)

Sources & evidence

ORD record
ord-934c8e3d13be4a2f879060ddf8ada55a
Source dataset
uspto-grants-2016_04
Patent number
US09309245B2

Reaction notes

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