Sodium hydride → 1-(2,4-dichlorophenyl)-2-(4(R)-benzyloxy-2(R)-methoxy-3,4,5,6-tetrahydro-2H-pyran-6(S)-yl)ethyl phenyl sulfone

HRID 1719628Notes

Reaction equation

HRID 1719628 reaction equation
[H-].[Na+].[C:3]1([S:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:21]([O:28][C@@H:29]1[CH2:34][C@@H:33]([CH2:35]I)[O:32][C@@H:31]([O:37][CH3:38])[CH2:30]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C=O)C>[C:3]1([S:9]([CH:12]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[Cl:20])[CH2:35][C@H:33]2[O:32][C@@H:31]([O:37][CH3:38])[CH2:30][C@H:29]([O:28][CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:34]2)(=[O:11])=[O:10])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 20191362HCID 20191362, compoundHCID 56615162(2R,4R,6S)-4-benzyloxy-6-iodomethyl-2-methoxy-3,4,5,6-tetrahydro-2H-pyran

Product 1

HCID 228261981-(2,4-dichlorophenyl)-2-(4(R)-benzyloxy-2(R)-methoxy-3,4,5,6-tetrahydro-2H-pyran-6(S)-yl)ethyl phenyl sulfoneYield 68.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of sodium hydride (0.030 g of 50% NaH in mineral oil) in dry DMF (0.5 ml) under nitrogen is added 2,4-dichlorobenzyl phenyl sulfone (0.18 g; 0.6 mmole) as the crystalline solid all at once. The reaction mixture is stirred at room temperature under nitrogen under hydrogen evolution ceases (50 min.) A solution of (2R,4R,6S)-4-benzyloxy-6-iodomethyl-2-methoxy-3,4,5,6-tetrahydro-2H-pyran (0.109 g; 0.3 mmole) in dry DMF (0.4 ml) is added by syringe through a septum. The reaction is stirred for 2.5 hours at room temperature and then partitioned between ether (100 ml) and water (20 ml). The ether layer is extracted with water (4×20 ml), dried (MgSO4), filtered, and the solvent evaporated in vacuo to leave 0.24 g of crude product. Flash chromatography of this product on silica gel with a 30 mm×130 mm column, eluting with 2% (by volume) acetone in methylene chloride, gives 40 mg of the major diastereoisomer and 10 mg of the minor diastereoisomer and 60 mg of a mixture of the two with a total of 110 mg of 1-(2,4-dichlorophenyl)-2-(4(R)-benzyloxy-2(R)-methoxy-3,4,5,6-tetra-hydro-2H-pyran-6(S)-yl)ethyl phenyl sulfone.

Workup

  1. additionis added by syringe through a septum
  2. custompartitioned between ether (100 ml) and water (20 ml)
  3. extractionThe ether layer is extracted with water (4×20 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customto leave 0.24 g of crude product
  8. washFlash chromatography of this product on silica gel with a 30 mm×130 mm column, eluting with 2% (by volume) acetone in methylene chloride

Sources & evidence

ORD record
ord-0743556017b34ca39331f372a6218579
Source dataset
uspto-grants-1985_09
Patent number
US04540796

Reaction notes

Loading…