Sodium hydride → HCID 68792288, compound

HRID 1713585Notes

Reaction equation

HRID 1713585 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:17])[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH3:16])=[CH:11][CH:10]=1.[H-].[Na+].[C:20]([O:23][C@@H:24]1[C@@H:29]([O:30][C:31](=[O:33])[CH3:32])[C@H:28]([O:34][C:35](=[O:37])[CH3:36])[C@@H:27]([CH2:38][O:39][C:40](=[O:42])[CH3:41])[O:26][C@@:25]1([O:56][CH3:57])[CH2:43][CH2:44]OS(C1C=CC(C)=CC=1)(=O)=O)(=[O:22])[CH3:21].[O-]C1C=CC=CC=1>CN(C=O)C.CCOC(C)=O>[C:20]([O:23][C@@H:24]1[C@@H:29]([O:30][C:31](=[O:33])[CH3:32])[C@H:28]([O:34][C:35](=[O:37])[CH3:36])[C@@H:27]([CH2:38][O:39][C:40](=[O:42])[CH3:41])[O:26][C@:25]1([CH2:43][CH2:44][O:17][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH3:16])=[CH:11][CH:10]=2)=[C:2]([Cl:1])[CH:3]=1)[O:56][CH3:57])(=[O:22])[CH3:21]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 119047PhenolateHCID 68790262HCID 68790262, compoundHCID 86621847HCID 86621847, compound

Product 1

HCID 68792288HCID 68792288, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

3-Chloro-4-(4-ethylbenzyl)phenol (15) (55 mg, 0.22 mmol) was dissolved in DMF (0.30 mL) and NaH (9 mg, 0.22 mmol) was added to the solution. After stirring for 5 min, a solution of (2S,3R,4S,5R,6R)-6-(acetoxymethyl)-2-methoxy-2-(2-(tosyloxy)ethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (17) (102 mg, 0.18 mmol in 200 μL DMF) was added to the phenoxide solution. After 2 h, the reaction was heated to 70° C. and stirred for 18 h. The reaction mixture was then diluted with EtOAc and washed with NaHCO3 (1×). The aqueous layer was back-extracted with EtOAc (2×). The organic layers were combined, dried (Na2SO4), concentrated onto celite and chromatographed over SiO2 (ISCO system, 0-60% EtOAc/hexanes) to provide an oil (19 mg, 17%). 1H NMR (300 MHz, CDCl3) δ ppm: 7.07 (m, 5H), 6.88 (d, J=2.4 Hz, 1H), 6.69 (dd, J=8.9, 2.6 Hz, 1H), 5.47 (t, J=9.6 Hz, 1H), 5.00-5.15 (m, 3H), 3.85-4.17 9 m, 6H), 3.32 (s, 3H), 2.61 (q, J=15, 7.5 Hz, 2H), 2.06 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H), 1.21 (t, J=7.5 Hz, 3H). LC/MS: tR=3.07 min, calcd for C32H39ClO11: 634.22, found 657.4 (M+Na)+.

Workup

  1. waitAfter 2 h
  2. stirringstirred for 18 h
  3. washwashed with NaHCO3 (1×)
  4. extractionThe aqueous layer was back-extracted with EtOAc (2×)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated onto celite
  7. customchromatographed over SiO2 (ISCO system, 0-60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ba98fa4cc53946ce9aaf2adb61338bf4
Source dataset
uspto-grants-2010_09
Patent number
US07795228B2

Reaction notes

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