Boron trifluoride etherate → diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate

HRID 522167Notes

Reaction equation

HRID 522167 reaction equation
B(F)(F)F.CCOCC.C([SiH](CC)CC)C.[CH2:17]([O:24][C@H:25]1[C@H:30]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C@H:29]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@H:28]([CH3:47])[O:27][C@@:26]1([CH2:49][P:50](=[O:57])([O:54][CH2:55][CH3:56])[O:51][CH2:52][CH3:53])O)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(#N)C>[CH2:17]([O:24][C@H:25]1[C@H:30]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C@H:29]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@H:28]([CH3:47])[O:27][C@@H:26]1[CH2:49][P:50](=[O:57])([O:51][CH2:52][CH3:53])[O:54][CH2:55][CH3:56])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 11786599diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate

Product 1

HCID 11238435diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonateYield 90.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Boron trifluoride diethyl etherate (0.079 mL, 0.644 mmol, commercially available from Sigma Aldrich) and triethylsilane (0.103 mL, 0.644 mmol, Sigma Aldrich) were added to a stirred solution of diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-2-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate (0.251 g, 0.429 mmol) in acetonitrile (2 mL) at 0° C. under an argon atmosphere. The reaction mixture was then stirred at 0° C. for 5 h. The reaction mixture was next partitioned between EtOAc and saturated aqueous sodium bicarbonate. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The resulting oil was purified by silica gel chromatography (30 to 100% EtOAc/hexanes gradient) to give diethyl (((2S,3S,4R,5R,6S)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-yl)methyl)phosphonate as a colorless oil (0.220 g, 90% yield). 1H NMR (400 MHz, CDCl3): δ ppm 1.14 (d, J=6.26 Hz, 3 H) 1.26 (td, J=7.04, 1.96 Hz, 6 H) 1.92 (td, J=15.75, 9.78 Hz, 1 H) 2.29 (ddd, J=19.95, 15.36, 1.47 Hz, 1 H) 3.53 (q, J=6.39 Hz, 1H) 3.56-3.70 (m, 4 H) 3.98-4.11 (m, 4 H) 4.63-4.77 (m, 4 H) 4.97 (dd, J=11.44, 1.86 Hz, 2 H) 7.26-7.39 (m, 15 H).

Workup

  1. customThe reaction mixture was next partitioned between EtOAc and saturated aqueous sodium bicarbonate
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting oil was purified by silica gel chromatography (30 to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-77c1706d569f4b73867cd52f4ce6ec98
Source dataset
uspto-grants-2016_05
Patent number
US09328134B2

Reaction notes

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