Boron trifluoride etherate → HCID 118045163, compound

HRID 2284876Notes

Reaction equation

HRID 2284876 reaction equation
[C:1]([O:4][CH2:5][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@@H:9]([O:20][C:21](=[O:23])[CH3:22])[C@H:8]([N:24]2[C:32]3[C:27](=[C:28]([CH3:33])[CH:29]=[CH:30][CH:31]=3)[C:26]([CH:34]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[CH:38][CH:37]=3)O)=[CH:25]2)[O:7]1)(=[O:3])[CH3:2].C([SiH](CC)CC)C.B(F)(F)F.CCOCC.C([O-])(O)=O.[Na+]>C(#N)C.ClCCl.O>[C:1]([O:4][CH2:5][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@@H:9]([O:20][C:21](=[O:23])[CH3:22])[C@H:8]([N:24]2[C:32]3[C:27](=[C:28]([CH3:33])[CH:29]=[CH:30][CH:31]=3)[C:26]([CH2:34][C:36]3[CH:37]=[CH:38][C:39]([O:42][CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[CH:40][CH:41]=3)=[CH:25]2)[O:7]1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 516892Sodium BicarbonateHCID 118045321HCID 118045321, compound

Product 1

HCID 118045163HCID 118045163, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Cool a mixture of [(2R,3R,4S,5R,6R)-3,4,5-triacetoxy-6-[3-[(4-benzyloxyphenyl)-hydroxy-methyl]-4-methyl-indol-1-yl]tetrahydropyran-2-yl]methyl acetate (1.52 moles; 1.55 kg) in acetonitrile (6.19 L) and dichloromethane (6.19 L) in an brine/ice bath until the internal temperature is −5° C., then add triethylsilane (3.79 moles; 607 mL) over 2 minutes. Add boron trifluoride etherate (3.79 moles; 479 mL) dropwise maintaining the internal temperature below +5° C. Stir the mixture in the ice bath for 30 mins. Carefully add a mixture of NaHCO3 (saturated aqueous solution; 5 L) and water (4 L). Separate the organic phase and wash with water then brine then dry over MgSO4, filter, and concentrate under reduced pressure to afford a mixture of the title compound and compounds with one or more of the acetyl groups missing. Dissolve the residue in dichloromethane (1.86 L) and add acetic acid anhydride (7.58 moles; 716 mL) and N,N-dimethyl-4-pyridinamine, (75.78 mmoles; 9.26 g). Warm the mixture to 40° C. and gently agitate to aid dissolution then stir the mixture for 1 hour at room temperature. Concentrate the mixture under reduced pressure and slurry the residue in MTBE (6 L) overnight. Collect the solid by filtration and dry in an oven at 60° C. under reduced pressure to afford the title compound (692.8 g; 70% yield) mass spectrum (m/z): 658.3 (M+1) and 680.2 (M+23).

Workup

  1. temperatureCool
  2. customis −5° C.
  3. additionCarefully add
  4. customSeparate the organic phase
  5. washwash with water
  6. dry with materialbrine then dry over MgSO4
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customto afford

Sources & evidence

ORD record
ord-26da3573fbcc45e5aa8f044a9f2802e2
Source dataset
uspto-grants-2015_09
Patent number
US09145437B2

Reaction notes

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