Diisopropylethylamine → L-Phenylalanine, methyl ester

HRID 1976948Notes

Reaction equation

HRID 1976948 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11](NC(C2C(Cl)=CC=CC=2Cl)=O)=[CH:10][CH:9]=1)[NH2:6].ClC1C=CC=C(C)C=1C(O)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 888702-Chloro-6-methylbenzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23383932methyl (2S)-2-amino-3-{4-[(2,6-dichlorobenzoyl)amino]phenyl}propionate hydrochloride

Product 1

HCID 736234L-Phenylalanine, methyl esterYield 137.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-L-phenylalanine methyl ester hydrochloride (1.23 g, 3.05 mmol), 2-chloro-6-methylbenzoic acid (0.50 g, 2.93 mmol), HBTU (1.16 g, 3.05 mmol) and DIPEA (1.33 mL, 7.6 mmol) in DMF (12 mL) was stirred 15 hr at room temperature. The mixture was diluted with ethyl acetate (250 mL) and was washed with 0.5 N HCl (2×80 mL), sat. sodium bicarbonate (2×80 mL) and brine (2×80 mL) and was dried (Na2SO4). The solution was filtered and concentrated to a yellow gum which was crystallized from ethyl acetate-hexane to give N-(2-chloro-6-methylbenzoyl)-4-[(2,6-dichlorophenyl)carbonyl]amino]-L-phenylalanine methyl ester (0.75 g), suitable for use in the next step. The mother liquors were concentrated and purified by silica gel chromatography eluting with 1:1 ethyl acetate:hexane to give an additional 0.625 g.

Workup

  1. washwas washed with 0.5 N HCl (2×80 mL), sat. sodium bicarbonate (2×80 mL) and brine (2×80 mL)
  2. dry with materialwas dried (Na2SO4)
  3. filtrationThe solution was filtered
  4. concentrationconcentrated to a yellow gum which
  5. customwas crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-015df0883fc949639c7ac9855f3fcc9f
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

Loading…