Lithium Hydroxide → HCID 89555423, compound

HRID 928647Notes

Reaction equation

HRID 928647 reaction equation
[CH3:1][C:2]1([CH3:16])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[O:3]1.Br[CH2:18][C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=1)[C:22]([O:24]C)=O.C(=O)([O-])[O-].[K+].[K+].[OH-].[Li+].Cl.C(N=C=NCCCN(C)C)C.CCN=C=NCCCN(C)C.[NH:60]1[CH2:71][CH2:70][CH2:69][C@H:61]1[C:62]([O:64]C(C)(C)C)=[O:63].C(N(CC)CC)C>C(OCC)(=O)C.ClCCl.O.CO.CN(C=O)C>[CH3:8][C:6]1([CH3:7])[C:2]([CH3:16])([CH3:1])[O:3][B:4]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:18][C:19]3[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=3)[C:22]([N:60]3[CH2:71][CH2:70][CH2:69][C@H:61]3[C:62]([OH:64])=[O:63])=[O:24])=[CH:11][CH:10]=2)[O:5]1

Participants

14

Reactant 8

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 517981Methyl 3-(bromomethyl)benzoateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27346244-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 6453108L-Proline 1,1-dimethylethyl ester

Product 1

HCID 89555423HCID 89555423, compoundYield 88%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

DMF (125 mL) was added to 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (8.46 g, 38 mmol), methyl 3-(bromomethyl)benzoate (8.8 g, 38 mmol), and potassium carbonate (10.6 g, 77 mmol), and stirred at room temperature overnight. The resultant was diluted with ethyl acetate, washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. To the resulting residue, methanol (150 mL), water (30 mL), and lithium hydroxide (4.8 g, 114 mmol) were added, and stirred at room temperature overnight. After the solvent was distilled away under reduced pressure, the resultant was diluted with ethyl acetate, then washed with 1 N hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. To the resulting residue, dichloromethane (150 mL), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (hereinafter, WSC) (7.34 g, 38.2 mmol), tert-butyl L-prolinate (7.95 g, 38.2 mmol), and triethylamine (9.65 mL, 69.4 mmol) were added, and stirred at room temperature overnight. The resultant was washed with water, 1 N hydrochloric acid, 1 N sodium hydroxide, and saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure, and the residue was purified by silica gel chromatography (hexane/ethyl acetate). To the resulting compound, TFA (150 mL) was added, and stirred at room temperature for 3 hours. The solvent was distilled away under reduced pressure to thus obtain the title compound.

Workup

  1. washwashed with water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. distillationThe solvent was distilled away under reduced pressure
  4. stirringstirred at room temperature overnight
  5. distillationAfter the solvent was distilled away under reduced pressure
  6. additionthe resultant was diluted with ethyl acetate
  7. washwashed with 1 N hydrochloric acid and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled away under reduced pressure
  10. stirringstirred at room temperature overnight
  11. washThe resultant was washed with water, 1 N hydrochloric acid, 1 N sodium hydroxide, and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. distillationThe solvent was distilled away under reduced pressure
  14. customthe residue was purified by silica gel chromatography (hexane/ethyl acetate)
  15. additionTo the resulting compound, TFA (150 mL) was added
  16. stirringstirred at room temperature for 3 hours
  17. distillationThe solvent was distilled away under reduced pressure

Sources & evidence

ORD record
ord-b64c466cbb5c4bf885467177299d6ae1
Source dataset
uspto-grants-2016_03
Patent number
US09290487B2

Reaction notes

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