Phenylalanine, 1,1-dimethylethyl ester → 2-[(3-Bromo-thiophen-2-ylmethyl)-amino]-3-phenyl-propionic acid tert-butyl ester

HRID 2179922Notes

Reaction equation

HRID 2179922 reaction equation
[C:1]([O:5][C:6](=[O:16])[CH:7]([NH2:15])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[Br:17][C:18]1[CH:22]=[CH:21][S:20][C:19]=1[CH:23]=O.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>C(O)C.C(O)(=O)C>[C:1]([O:5][C:6](=[O:16])[CH:7]([NH:15][CH2:23][C:19]1[S:20][CH:21]=[CH:22][C:18]=1[Br:17])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 262751Phenylalanine, 1,1-dimethylethyl esterHCID 516892Sodium BicarbonateHCID 27970793-Bromothiophene-2-carboxaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 207793132-[(3-Bromo-thiophen-2-ylmethyl)-amino]-3-phenyl-propionic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent

Procedure

To a stirred solution of 2-Amino-3-phenyl-propionic acid tert-butyl ester (50.6 mg, 0.229 mmol) in ethanol (1 mL), were added 3-Bromo-thiophene-2-carbaldehyde (50 mg, 0.208 mmol.) and acetic acid (21 μL). The reaction mixture was stirred at room temperature under nitrogen for 2 hrs as the progress of imine formation was monitored by TLC. Then, sodium cyanoborohydride (20 mg, 0.312 mmol) was added. The mixture was acidified with sodium bicarbonate and then extracted with dichloromethane. After removal of the solvent, the crude product was purified by silica plate (hexane/ethylacetate 90%:10%) to give 2-[(3-Bromo-thiophen-2-ylmethyl)-amino]-3-phenyl-propionic acid tert-butyl ester in 80% yield: 1H NMR (Varian 400 MHz, CDCl3) δ7.23 (m, 6H, ArH), 6.90 (d, 1H, J=5.3 Hz, thiophenH), 4.00 (d, 1H, J=14.6 Hz, NCH2), 3.85 (d, 1H, J=14.6 Hz, NCH2), 3.48 (m, 1H, CHCH2), 3.00 (m, 2H, CHCH2), 1.37 (s, 9H, tBu).

Workup

  1. extractionextracted with dichloromethane
  2. customAfter removal of the solvent
  3. customthe crude product was purified by silica plate (hexane/ethylacetate 90%:10%)

Sources & evidence

ORD record
ord-9799c59f3f764fdfac479449627414cf
Source dataset
uspto-grants-2005_05
Patent number
US06887877B2

Reaction notes

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