Boron trifluoride etherate → HCID 59799035, compound

HRID 911237Notes

Reaction equation

HRID 911237 reaction equation
[C:1]([C:4]1[CH:20]=[CH:19][C:7]2[CH2:8][CH2:9][N:10]([C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[CH2:11][CH2:12][C:6]=2[C:5]=1[OH:21])(=O)[CH3:2].B(F)(F)F.CCOCC.C([BH3-])#N.[Na+].C([SiH](CC)CC)C>C1COCC1>[CH2:1]([C:4]1[CH:20]=[CH:19][C:7]2[CH2:8][CH2:9][N:10]([C:13](=[O:18])[C:14]([F:17])([F:15])[F:16])[CH2:11][CH2:12][C:6]=2[C:5]=1[OH:21])[CH3:2]

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 12052TriethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 59799040HCID 59799040, compound

Product 1

HCID 59799035HCID 59799035, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Under nitrogen dissolve 7-acetyl-6-hydroxy-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.0 g, 3.32 mmol) in anhydrous THF (100 mL). Cool the solution to 0° C., add boron trifluoride diethyl etherate (3.4 mL, 26.6 mmol) and sodium cyanoborohydride (836 mg, 13.3 mmol). Remove the ice bath and stir for 5 h at ambient temperature. Dilute with EtOAc and wash with 0.1N aqueous HCl. Separate the organic layer, dry over Na2SO4, filter and concentrate in vacuo. MS (ES−) m/z: 302 (M−H)−. Mix the residue with trifluoroacetic acid (40 mL) and anhydrous DCM (50 mL) under nitrogen. Cool to 0° C. in an ice bath and add triethyl silane (3.5 mL, 21.9 mmol). After 15 min, remove the ice bath and stir at ambient temperature for 16 h. Concentrate in vacuo and purify by chromatography on silica gel eluting with EtOAc/hexane (1:9) to obtain the desired intermediate (698 mg, 73%). MS (ES−) m/z: 286 (M−H)−.

Workup

  1. customRemove the ice bath
  2. additionDilute with EtOAc
  3. washwash with 0.1N aqueous HCl
  4. customSeparate the organic layer
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. additionMix the residue with trifluoroacetic acid (40 mL) and anhydrous DCM (50 mL) under nitrogen
  9. temperatureCool to 0° C. in an ice bath
  10. waitAfter 15 min
  11. customremove the ice bath
  12. stirringstir at ambient temperature for 16 h
  13. concentrationConcentrate in vacuo
  14. custompurify by chromatography on silica gel eluting with EtOAc/hexane (1:9)

Sources & evidence

ORD record
ord-5642517910f341719dacbb60f3f107b2
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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