Methanol → (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(difluoromethoxy)ethyl)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

HRID 425065Notes

Reaction equation

HRID 425065 reaction equation
C([O:8][C@H:9]1[C@H:14]([O:15]CC2C=CC=CC=2)[C@@H:13]([O:23]CC2C=CC=CC=2)[C@H:12]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([CH2:45][CH2:46][O:47][CH:48]([F:50])[F:49])=[CH:41][CH:40]=3)[CH:32]=2)[O:11][C@@H:10]1[CH2:51][O:52]CC1C=CC=CC=1)C1C=CC=CC=1.CO.O1CCCC1>[Pd].ClC1C=CC=CC=1Cl>[Cl:37][C:34]1[CH:35]=[CH:36][C:31]([C@H:12]2[C@H:13]([OH:23])[C@@H:14]([OH:15])[C@H:9]([OH:8])[C@@H:10]([CH2:51][OH:52])[O:11]2)=[CH:32][C:33]=1[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][CH2:46][O:47][CH:48]([F:50])[F:49])=[CH:41][CH:40]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 8028TetrahydrofuranHCID 57684694(2R,3R,4R,5S,6S)-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-6-(4-chloro-3-(4-(2-(difluoromethoxy)ethyl)benzyl)phenyl)tetrahydro-2H-pyran

Product 1

HCID 25195623(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(difluoromethoxy)ethyl)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triolYield 64%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 72391,2-DichlorobenzeneSolvent

Procedure

(2R,3R,4R,5S,6S)-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-6-(4-chloro-3-(4-(2-(difluoromethoxy)ethyl)benzyl)phenyl)tetrahydro-2H-pyran (intermediate BM) was taken up in a mixture of 4:1 methanol:tetrahydrofuran (0.5 mL) and 9.6 μL of 1,2-dichlorobenzene was added followed by palladium on charcoal (10%, 5 mg). The mixture was stirred at room temperature under a hydrogen balloon for 30 min. The mixture was passed through a short Celite® pad to remove the catalyst, and the pad was washed with methanol (1 mL). Solvent was evaporated and the product was purified by TLC using 8:1 dichloromethane:methanol to obtain compound BN (2.5 mg, yield 64%). 1H NMR (300 MHz, CDCl3): δ 7-33-7.11 (m, 7H), 6.30 (t, JC-F=75.6 Hz, 1H), 4.13 (d, J=9 Hz, 1H), 4.04 (m, 4 H), 3.86-3.80 (m, 3H), 3.64 (t, J=4.5, 6.6 Hz, 2H), 3.47-3.41 (m, 2H), 2.90 (t, J=6.9, 7.2 Hz, 2H); LC-ESI-MS (m/z): 457 (M−H).

Workup

  1. customto remove the catalyst
  2. washthe pad was washed with methanol (1 mL)
  3. customSolvent was evaporated
  4. customthe product was purified by TLC
  5. custommethanol to obtain compound BN (2.5 mg, yield 64%)

Sources & evidence

ORD record
ord-d5e429db8c984eb1ba237fca87f0837e
Source dataset
uspto-grants-2012_01
Patent number
US08106021B2

Reaction notes

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