Tetrabutylammonium Fluoride → [(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6-methoxy-tetrahydropyran-2-yl]methanol

HRID 1055599Notes

Reaction equation

HRID 1055599 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][CH2:55][C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)=[CH:50][CH:49]=3)[CH:41]=2)([O:38][CH3:39])[O:9]1)(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>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:49]=[CH:50][C:51]([O:54][CH2:55][C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)=[CH:52][CH:53]=3)[CH:41]=2)([O:38][CH3:39])[O:9][C@@H:8]1[CH2:7][OH:6])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 131736396tert-butyl-dimethyl-[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]silane

Product 1

HCID 131736395[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6-methoxy-tetrahydropyran-2-yl]methanolYield 27.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl-dimethyl-[[(2R,3R,4S,5R,6S)-3,4,5-tribenzyloxy-6-[3-[(4-benzyloxyphenyl)methyl]-4-chloro-phenyl]-6-methoxy-tetrahydropyran-2-yl]methoxy]silane 25g (2.26 g, 2.56 mmol) in anhydrous tetrahydrofuran (20 mL) was added tetrabutylammonium fluoride (5.12 mL, 5.12 mmol, 1 M in tetrahydrofuran) at room temperature. The mixture was stirred at room temperature for 12 hours, then quenched with water (60 mL) and partitioned. The aqueous layer was extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with water (100 mL×2) and saturated aqueous sodium chloride (100 mL×2) in turn, 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)=10/1 to give the title compound 25h as a light yellow solid (0.54 g, 27.4%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, DMSO-d6) δ (ppm): 7.46 (m, 2H), 7.42 (m, 2H), 7.35-7.24 (m, 17H), 7.01 (m, 4H), 6.84 (m, 2H), 5.02 (s, 2H), 4.82-4.75 (m, 3H), 4.69 (d, 1H), 4.41 (d, 1H), 4.04 (m, 1H), 3.97 (t, 1H), 3.88 (d, 1H), 3.77 (d, 1H), 3.70 (m, 3H), 3.53 (m, 1H), 3.23 (d, 1H), 2.97 (s, 3H).

Workup

  1. customquenched with water (60 mL)
  2. custompartitioned
  3. extractionThe aqueous layer was extracted with ethyl acetate (100 mL×2)
  4. washThe combined organic layers were washed with water (100 mL×2) and saturated aqueous sodium chloride (100 mL×2) in turn
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by silica gel chromatography
  9. washeluted with PE/EtOAc(v/v)=10/1

Sources & evidence

ORD record
ord-00968a1b19bb4cdeb84337a8c0e14af5
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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