Methanol → (S)-methyl 2-amino-3-(4-cyanophenyl)propanoate

HRID 716386Notes

Reaction equation

HRID 716386 reaction equation
C(OC([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=O)(C)(C)C.S(Cl)(Cl)=O.[CH3:26]O>>[NH2:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=1)[C:10]([O:12][CH3:26])=[O:11]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 7020841N-(tert-Butoxycarbonyl)-4-cyano-L-phenylalanine

Product 1

HCID 54521608(S)-methyl 2-amino-3-(4-cyanophenyl)propanoateYield 97%

Procedure

To a solution of (S)-2-((tert-butoxycarbonyl)amino)-3-(4-cyanophenyl)propanoic acid (1.0 g, 3.44 mmol) in MeOH (20 mL) at 0° C. was slowly added thionyl chloride (818.1 mg, 6.89 mmol) over 1 h. The reaction was warmed to RT and stirred for 1 h. The solvent was removed under reduced pressure. The reaction mixture was washed with saturated aqueous NaHCO3 (20 ml) and extracted with DCM (3×10 ml). The organic layer was dried over MgSO4 and concentrated. The crude product was purified by chromatography (EA/hexanes) to afford 789 mg (97%) of (S)-methyl 2-amino-3-(4-cyanophenyl)propanoate as the HCl salt. LCMS-ESI (m/z) calculated for C11H12N2O2: 204.1. found 205.0 [M+H]+, tR=3.25 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 3H), 7.83 (d, J=8.3 Hz, 2H), 7.51 (t, J=8.8 Hz, 2H), 4.37 (t, J=6.7 Hz, 1H), 3.68 (s, 3H), 3.23 (qd, J=14.4, 7.7 Hz, 2H).

Workup

  1. customat 0° C.
  2. customover 1 h
  3. customThe solvent was removed under reduced pressure
  4. washThe reaction mixture was washed with saturated aqueous NaHCO3 (20 ml)
  5. extractionextracted with DCM (3×10 ml)
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude product was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-0ff38afe3e434c119ec65c62c6e5d988
Source dataset
uspto-grants-2015_11
Patent number
US09187522B2

Reaction notes

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