Hydrochloric Acid → Methyl 1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-α-D-glucopyranoside

HRID 218984Notes

Reaction equation

HRID 218984 reaction equation
[CH:1](OC(C)C)(C)C.Br[C:9]1[CH:10]=[CH:11][C:12]([F:25])=[C:13]([CH:24]=1)[CH2:14][C:15]1[S:16][C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH:19]=1.C([Li])CCC.C[Si](C)(C)[O:33][C@@H:34]1[C@@H:40]([O:41][Si](C)(C)C)[C@H:39]([O:46][Si](C)(C)C)[C@@H:38]([CH2:51][O:52][Si](C)(C)C)[O:37][C:35]1=[O:36].Cl.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O.CO.C1(C)C=CC=CC=1.CCCCCC>[S:16]1[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH:19]=[C:15]1[CH2:14][C:13]1[CH:24]=[C:9]([C@@:35]2([O:37][C@H:38]([CH2:51][OH:52])[C@@H:39]([OH:46])[C@H:40]([OH:41])[C@H:34]2[OH:33])[O:36][CH3:1])[CH:10]=[CH:11][C:12]=1[F:25]

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 7914Diisopropyl EtherHCID 11430Potassium CarbonateHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 66608287HCID 66608287, compoundHCID 178418339Butyllithium

Product 1

HCID 68587726Methyl 1-C-[3-(benzo[b]thien-2-ylmethyl)-4-fluorophenyl]-α-D-glucopyranoside

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a toluene (32.5 ml)-diisopropyl ether (25 ml) solution of 2-(5-bromo-2-fluorobenzyl)-1-benzothiophene (5.0 g) was dropwise added a n-hexane solution (10 ml) of n-butyl lithium (1.6 M) at −43.5 to −33.3° C., followed by stirring for 10 minutes. To the reaction mixture was added, at −72.6 to −65.0° C., a toluene (17.5 ml) solution of 2,3,4,6-tetrakis-O-(trimethylsilyl)-D-glucono-1,5-lactone (8.0 g), followed by stirring for 6 hours. The reaction mixture was added to a methanol (25 ml) solution of an ethyl acetate solution (7.8 ml) of hydrogen chloride (4 M) at a temperature of 0° C. or lower, followed by stirring at 0° C. for 17 hours. The reaction mixture was added to a water (35 ml) solution of potassium carbonate (1.29 g). Thereto was added ethyl acetate, followed by extraction. The aqueous layer was extracted with toluene (20 ml)-ethyl acetate (10 ml). The organic layers obtained by extraction were combined and subjected to vacuum distillation to distil off the solvent until the reside became 40 ml. Toluene (25 ml) was added to the residue and the mixture was subjected to vacuum distillation to distil off the solvent until the residue became 40 ml. This operation of adding toluene to the residue and subjecting the mixture to vacuum distillation to distil off the solvent, was repeated twice to obtain methyl 1-C-[3-(1-benzothien-2-ylmethyl)-4-fluorophenyl]-α-glucopyranoside as a toluene solution.

Workup

  1. additionTo the reaction mixture was added, at −72.6 to −65.0° C.
  2. stirringby stirring for 6 hours
  3. stirringby stirring at 0° C. for 17 hours
  4. extractionfollowed by extraction
  5. extractionThe aqueous layer was extracted with toluene (20 ml)-ethyl acetate (10 ml)
  6. customThe organic layers obtained by extraction
  7. distillationsubjected to vacuum distillation
  8. customto distil off the solvent until the reside
  9. additionToluene (25 ml) was added to the residue
  10. distillationthe mixture was subjected to vacuum distillation
  11. customto distil off the solvent until the residue
  12. distillationto vacuum distillation
  13. customto distil off the solvent

Sources & evidence

ORD record
ord-41bf7b8c400a46448c6c9105eba2398d
Source dataset
uspto-grants-2012_06
Patent number
US08198464B2

Reaction notes

Loading…