Sodium Hydroxide → (S)-3-(tert-butyldimethylsilanyloxy)-1-(2-fluorophenyl)propylamine

HRID 339873Notes

Reaction equation

HRID 339873 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[NH2:7][C@H:8]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[F:19])[CH2:9][C:10]([OH:12])=O.[OH-].[Na+].[C:22]([Si:26](Cl)([CH3:28])[CH3:27])([CH3:25])([CH3:24])[CH3:23]>C1COCC1.C(Cl)Cl.C(N(CC)CC)C.O>[Si:26]([O:12][CH2:10][CH2:9][C@H:8]([NH2:7])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[F:19])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:28])[CH3:27]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 28928tert-Butyldimethylsilyl chlorideHCID 1481546(S)-3-Amino-3-(2-fluorophenyl)propanoic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 68292582(S)-3-(tert-butyldimethylsilanyloxy)-1-(2-fluorophenyl)propylamineYield 58,627.398%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

Under inert gas, 2.80 g of lithium aluminum hydride were added in portions to a suspension of 0.97 g of (S)-3-amino-3-(2-fluorophenyl)propionic acid in 80 ml of THF, and the reaction mixture was then stirred at a temperature of 50° C. for 3 hours. 3 ml of water, 1 ml of 12 N aqueous sodium hydroxide solution and another 10 ml of water were added and the mixture was stirred for 10 minutes. The precipitate was filtered off, the filtrate was concentrated by rotary evaporation, the residue was dissolved once again in methylene chloride, and the solution was dried over MgSO4 and concentrated by rotary evaporation. For further reaction, a solution of the residue in methylene chloride was admixed with 2.22 ml of triethylamine and 1.20 g of tert-butylchlorodimethylsilane. After stirring at room temperature overnight, the reaction solution was washed with aqueous sodium hydrogencarbonate solution, dried over MgSO4 and concentrated by rotary evaporation. The crude product was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined and concentrated by rotary evaporation. This gave the product (880 g) with a molecular weight of 283.5 g/mol (C15H26FNOSi); MS (ESI): m/e=284 (M+H+).

Workup

  1. stirringthe mixture was stirred for 10 minutes
  2. filtrationThe precipitate was filtered off
  3. concentrationthe filtrate was concentrated by rotary evaporation
  4. dissolutionthe residue was dissolved once again in methylene chloride
  5. dry with materialthe solution was dried over MgSO4
  6. concentrationconcentrated by rotary evaporation
  7. customFor further reaction
  8. stirringAfter stirring at room temperature overnight
  9. washthe reaction solution was washed with aqueous sodium hydrogencarbonate solution
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated by rotary evaporation
  12. customThe crude product was purified by means of normal phase chromatography
  13. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-ca7f9cd627824e89acd6989ebd03f0fe
Source dataset
uspto-grants-2014_11
Patent number
US08895547B2

Reaction notes

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