Benzo(B)Thiophene-2-Boronic Acid → HCID 68683394, compound

HRID 505443Notes

Reaction equation

HRID 505443 reaction equation
[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH:3]1[CH:4]=[C:5](OS(C(F)(F)F)(=O)=O)[CH2:6]2.[S:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[CH:20]=[C:19]1B(O)O.C(=O)([O-])[O-].[K+].[K+].[Cl-].[Li+].[C:38]([OH:47])(=[O:46])[C@H:39]([C@@H:41]([C:43]([OH:45])=[O:44])[OH:42])[OH:40]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C.O.COCCOC>[C:38]([OH:47])(=[O:46])[C@H:39]([C@@H:41]([C:43]([OH:45])=[O:44])[OH:42])[OH:40].[S:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[CH:20]=[C:19]1[C:5]1[CH2:6][CH:7]2[N:2]([CH3:1])[CH:3]([CH2:9][CH2:8]2)[CH:4]=1

Participants

10

Reactant 5

HCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 11430Potassium CarbonateHCID 433294Lithium ChlorideHCID 439655D-Tartaric acidHCID 11993054(-)-8-methyl-3-(trifluoromethylsulfonyloxy)-8-aza-bicyclo[3.2.1]oct-2-ene

Product 1

HCID 68683394HCID 68683394, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of (−)-8-methyl-3-(trifluoromethylsulfonyloxy)-8-azabicyclo[3.2.1]oct-2-ene, (4.64 g, 17.1 mmol), 1,2-dimethoxyethane (100 ml), 2-benzothienyl boronic acid (4.5 g, 25 mmol), potassium carbonate (9.2 g, 66.6 mmol), lithium chloride (2.0 g, 47.2 mmol) and water (50 ml) was bubbled through with argon for 10 min. Pd(PPh3)4 (0.17 g, 0.13 mmol) was added followed by reflux for 45 min. The mixture was allowed to cool to room temperature. Water (100 ml) was added followed by extraction with diethyl ether (2×50 ml). The organic phase was washed with water (2×50 ml). The organic phase was dried and evaporated. The hydrochloric acid salt was precipitated by addition of hydrochloric acid (4 M) solved in ethanol (5 ml, 96%). Addition water (50 ml) and concentrated ammonia (50 ml) followed by extraction with dichloromethane (2×50 ml) gave the free base. (4.09 g, 100% from the salt) [α]D25=(−)-46.3°. The tartaric acid salt was prepared by adding D-tartaric acid (2.4 g, 16 mmol) to a mixture of the free base and ethanol (96%) at reflux. The mixture was allowed to cool overnight and was isolated by filtration. Yield 5.06 g (12.47 mmol), chiral HPLC (−) 94.9% and (+) 5.1%. Recrystallization of 4.85 g (11.9 mmol) from ethanol (150 ml, 96%) yielded (3.26 g, 8.0 mmol), chiral HPLC (−) 97.9% and (+) 2.1%. Mp 67.6-76.0° C.

Workup

  1. customwas bubbled through with argon for 10 min
  2. temperatureby reflux for 45 min
  3. extractionfollowed by extraction with diethyl ether (2×50 ml)
  4. washThe organic phase was washed with water (2×50 ml)
  5. customThe organic phase was dried
  6. customevaporated
  7. customThe hydrochloric acid salt was precipitated by addition of hydrochloric acid (4 M)
  8. additionAddition water (50 ml) and concentrated ammonia (50 ml)
  9. extractionfollowed by extraction with dichloromethane (2×50 ml)
  10. customgave the free base
  11. custom-46.3°
  12. temperatureat reflux
  13. temperatureto cool overnight
  14. customwas isolated by filtration
  15. customRecrystallization of 4.85 g (11.9 mmol) from ethanol (150 ml, 96%)
  16. customyielded (3.26 g, 8.0 mmol), chiral HPLC (−) 97.9%

Sources & evidence

ORD record
ord-39228236c38b427cab8f27ebf9c07719
Source dataset
uspto-grants-2010_08
Patent number
US07781456B2

Reaction notes

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