Dichloromethane → HCID 131736645, compound

HRID 1481622Notes

Reaction equation

HRID 1481622 reaction equation
[Si:1]([O:8][C@@H:9]1[C@@H:17]([CH2:18][OH:19])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:20]([CH2:28][CH3:29])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[S:14]2)[C@@H:10]1[F:30])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:31](Cl)Cl>C1COCC1>[Si:1]([O:8][C@@H:9]1[C@@H:17]([C@@H:18]([OH:19])[CH3:31])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:20]([CH2:28][CH3:29])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[S:14]2)[C@@H:10]1[F:30])([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 123998680HCID 123998680, compound

Product 1

HCID 131736645HCID 131736645, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl (3aR,5R,6R,7S,7aR)-6-(tert-butyldimethylsilyloxy)-7-fluoro-5-(hydroxymethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl(ethyl)carbamate (600 mg, 1.3 mmol) in DCM (30 mL) was added DMP (806 mg, 1.9 mmol) at 0° C. After stirring at room temperature for 2 h, the reaction was quenched with mixed saturated aqueous NaHCO3 (20 mL) and Na2S2O3 (20 mL). The resulting solution was extracted with DCM (3×30 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum to give the crude aldehyde. The aldehyde was dissolved in THF (30 mL), treated with MeMgC1 (3 M in THF, 1.1 mL, 3.3 mmol) at 0° C.˜25° C. for 3 h. The reaction was then quenched with H2O (50 mL) and extracted with EtOAc (3×40 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was purified by a silica gel column, eluted with 3%-30% EtOAc in petroleum ether to give tert-butyl (3aR,5R,6R,7S,7aR)-6-(tert-butyldimethylsilyloxy)-7-fluoro-5-((S)-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl(ethyl)carbamate as a yellow oil (355 mg, 57% of 2 steps). (ES, m/z) [M+H]+ 479.0; 1H NMR (300 MHz, CDCl3) δ 6.20-6.14 (m, 1H), 4.95-4.65 (m, 1H), 4.44-4.25 (m, 2H), 4.08-3.79 (m, 4H), 1.51 (s, 9H), 1.25-1.14 (m, 6H), 0.87 (s, 9H), 0.12-0.06 (m, 6H).

Workup

  1. customthe reaction was quenched with mixed saturated aqueous NaHCO3 (20 mL) and Na2S2O3 (20 mL)
  2. extractionThe resulting solution was extracted with DCM (3×30 mL)
  3. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated under vacuum
  5. customto give the crude aldehyde
  6. customThe reaction was then quenched with H2O (50 mL)
  7. extractionextracted with EtOAc (3×40 mL)
  8. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by a silica gel column
  11. washeluted with 3%-30% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-b19d162f01994ea08a012f6c8d571c54
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

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