Formic Acid → (1S,2S,3S,4R,5S)-5-[4-Chloro-3-(4-ethoxy-benzyl)-phenyl]-1-chloromethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol

HRID 1185012Notes

Reaction equation

HRID 1185012 reaction equation
C(O[C@H]1[C@H](OCC2C=CC=CC=2)[C@@H](OCC2C=CC=CC=2)[C@]2(C3C=CC(Cl)=C(CC4C=CC(OCC)=CC=4)C=3)O[C@@]1(CF)CO2)C1C=CC=CC=1.C([O:59][C@H:60]1[C@H:66]([O:67]CC2C=CC=CC=2)[C@@H:65]([O:75]CC2C=CC=CC=2)[C@:64]2([C:84]3[CH:89]=[CH:88][C:87]([Cl:90])=[C:86]([CH2:91][C:92]4[CH:97]=[CH:96][C:95]([O:98][CH2:99][CH3:100])=[CH:94][CH:93]=4)[CH:85]=3)[O:83][C@@:61]1([CH2:101][Cl:102])[CH2:62][O:63]2)C1C=CC=CC=1.C(O)=O.C(OCC)(=O)C>C(O)C.O1CCCC1.[Pd]>[Cl:90][C:87]1[CH:88]=[CH:89][C:84]([C@@:64]23[O:83][C@@:61]([CH2:101][Cl:102])([CH2:62][O:63]2)[C@@H:60]([OH:59])[C@H:66]([OH:67])[C@H:65]3[OH:75])=[CH:85][C:86]=1[CH2:91][C:92]1[CH:93]=[CH:94][C:95]([O:98][CH2:99][CH3:100])=[CH:96][CH:97]=1

Participants

8

Reactant 4

HCID 284Formic AcidHCID 8857Ethyl AcetateHCID 67153908HCID 67153908, compoundHCID 67153916HCID 67153916, compound

Product 1

HCID 52931640(1S,2S,3S,4R,5S)-5-[4-Chloro-3-(4-ethoxy-benzyl)-phenyl]-1-chloromethyl-6,8-dioxa-bicyclo[3.2.1]octane-2,3,4-triol

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of a mixture of (1S,2S,3S,4R,5S)-2,3,4-tris-benzyloxy-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-1-fluoromethyl-6,8-dioxa-bicyclo[3.2.1]octane and (1S,2S,3S,4R,5S)-2,3,4-tris-benzyloxy-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-1-chloromethyl-6,8-dioxa-bicyclo[3.2.1]octane (50 mg, 0.07 mmol) and palladium black (50 mg, 0.38 mmol, Aldrich® high surface area) in ethanol (0.5 mL) and tetrahydrofuran (0.1 mL) was added formic acid (0.10 mL, 2.80 mmol) and the resulting mixture was stirred at room temperature for 1.5 hours. Ethyl acetate was added and the mixture was filtered through a short pad of Celite® and concentrated in vacuo. The crude material was purified by flash chromatography over silica gel using a 4 g redisep silica cartridge (eluting with a gradient of 50 to 100% ethyl acetate in heptane) to afford the title compound as a solid (8.6 mg; ˜80% pure, contaminated with some Example 8).

Workup

  1. filtrationthe mixture was filtered through a short pad of Celite®
  2. concentrationconcentrated in vacuo
  3. customThe crude material was purified by flash chromatography over silica gel using a 4 g redisep silica cartridge (
  4. washeluting with a gradient of 50 to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-8580082d7b594658bbbc70bed5c07bbd
Source dataset
uspto-grants-2014_03
Patent number
US08669380B2

Reaction notes

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