Ethyl Acetate → [(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methanol

HRID 1055572Notes

Reaction equation

HRID 1055572 reaction equation
C([Si](C)(C)[O:6][CH2:7][C@@H:8]1[C@@H:13]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@H:12]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:11]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@@:10]([C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[C:42]([CH2:47][C:48]3[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[C:50]([F:56])[C:49]=3[F:57])[CH:41]=2)([O:38][CH3:39])[O:9]1)(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>O1CCCC1>[CH2:15]([O:14][C@H:13]1[C@H:12]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@@H:11]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@@:10]([C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[C:42]([CH2:47][C:48]3[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[C:50]([F:56])[C:49]=3[F:57])[CH:41]=2)([O:38][CH3:39])[O:9][C@@H:8]1[CH2:7][OH:6])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 131736388tert-butyl-dimethyl-[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]silane

Product 1

HCID 68015196[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methanolYield 33.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl-dimethyl-[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]silane 21j (72.7 g, 86 mmol) in tetrahydrofuran (300 mL) was added tetrabutylammonium fluoride (172 mL, 172 mmol, 1 M in tetrahydrofuran) at room temperature. The mixture was stirred at room temperature for 12 hours, and then ethyl acetate was added (300 mL). The resulting mixture was washed with water (400 mL×4), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=20/1 to give the title compound 21k as yellow oil (21.0 g, 33.4%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.42-7.29 (m, 13H), 7.27-7.17 (m, 3H), 7.01 (m, 2H), 6.74-6.66 (m, 1H), 6.63-6.53 (m, 1H), 4.99-4.88 (m, 3H), 4.72 (m, 1H), 4.54 (d, 1H), 4.15-4.09 (m, 2H), 3.99-3.89 (m, 3H), 3.87 (s, 3H), 3.83 (d, 1H), 3.78-3.66 (m, 2H), 3.34 (d, 1H), 3.10 (s, 3H).

Workup

  1. washThe resulting mixture was washed with water (400 mL×4)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe residue was purified by silica gel chromatography
  6. washeluted with PE/EtOAc(v/v)=20/1

Sources & evidence

ORD record
ord-778c60f6824245e99f633b928214fe61
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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