Sulfuric acid magnesium salt (1:1) → 4-[(Benzofuran-6-ylmethyl)-amino]-butyric acid ethyl ester

HRID 408590

Reaction equation

HRID 408590 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:10])[CH2:6][CH2:7][CH2:8][NH2:9])[CH3:3].[O:11]1[C:15]2[CH:16]=[C:17]([CH:20]=O)[CH:18]=[CH:19][C:14]=2[CH:13]=[CH:12]1.[O-]S([O-])(=O)=O.[Mg+2].[BH4-].[Na+]>C1COCC1.CO>[CH2:2]([O:4][C:5](=[O:10])[CH2:6][CH2:7][CH2:8][NH:9][CH2:20][C:17]1[CH:18]=[CH:19][C:14]2[CH:13]=[CH:12][O:11][C:15]=2[CH:16]=1)[CH3:3]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 4311764Sodium borohydrideHCID 126496614-Aminobutyrate ethyl hydrochlorideHCID 14354086Benzofuran-6-carbaldehyde

Product 1

HCID 705564744-[(Benzofuran-6-ylmethyl)-amino]-butyric acid ethyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-amino-butyric acid ethyl ester hydrochloride (1 eq.) in THF was added TEA (2.5 eq.). The mixture was stirred 5 min at 20° C., then benzofuran-6-carbaldehyde (0.95 eq.) and MgSO4 (3 eq.) were added. The reaction was refluxed for 2 h, then cooled to 20° C. and filtered. The filtrate was added to a suspension of NaBH4 (2 to 6 eq.) in MeOH at −15° C. The reaction was stirred for 2 h at −15° C. The reaction was quenched with the addition of aqueous HCl 2N until pH=2. The aqueous layer was washed twice with EtOAc. The organic layers were discarded. Solid KOH was added to the aqueous layer. The crude was extracted three times with EtOAc. The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure at 20° C. The crude was purified by chromatography on silica gel (elution with DCM/MeOH: 95/5) to afford 4-[(benzofuran-6-ylmethyl)-amino]-butyric acid ethyl ester.

Workup

  1. temperatureThe reaction was refluxed for 2 h
  2. temperaturecooled to 20° C.
  3. filtrationfiltered
  4. stirringThe reaction was stirred for 2 h at −15° C
  5. customThe reaction was quenched with the addition of aqueous HCl 2N until pH=2
  6. washThe aqueous layer was washed twice with EtOAc
  7. additionSolid KOH was added to the aqueous layer
  8. extractionThe crude was extracted three times with EtOAc
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure at 20° C
  12. customThe crude was purified by chromatography on silica gel (elution with DCM/MeOH: 95/5)

Sources & evidence

ORD record
ord-ac60bff47ab3460f836ac051f1ee32e2
Source dataset
uspto-grants-2014_06
Patent number
US08759334B2

Linked notes

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