Methyl iodide → N-Boc-N-methyl-4-methoxy-L-phenylalanine

HRID 843561Notes

Reaction equation

HRID 843561 reaction equation
[NH:1]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8]C(O)=CC=1.[CH3:21]I.[H-].[Na+].[CH2:25]1[CH2:29][O:28][CH2:27][CH2:26]1>>[C:17]([O:16][C:14]([N:1]([CH3:21])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:26]=[CH:25][C:29]([O:28][CH3:27])=[CH:8][CH:9]=1)=[O:15])([CH3:18])([CH3:19])[CH3:20]

Participants

5

Reactant 4

HCID 6328Methyl iodideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-

Product 1

HCID 7016369N-Boc-N-methyl-4-methoxy-L-phenylalanineYield 90%

Conditions

Temperature
0 °C

Procedure

A solution of BocTyrOH (5.30 g, 18.8 mmol) and methyl iodide (2.57 mL, 41.4 mmol) in 80 mL of dry THF was cooled at 0° C. and sodium hydride (60% dispersion, 2.47 g, 62.0 mmol) was added. The reaction was allowed to stir at 0° C. for 1 hour, then at rt overnight. Excess sodium hydride was quenched by the dropwise addition of 10 mL of THF/H2O (1:1) and the solvents were removed in vacuo. After removal of the solvents, the deep orange gel was diluted with 30 mL of water and washed with pentane (2×30 mL). The aqueous phase was acidified with solid citric acrd (pH 2). Ethyl acetate was used for extraction. The combined extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with ethyl ether to afford the desired compound as a yellow oil (5.22 g, 90%); [α]29 D-15.7° (c 1.0, MeOH), Lit.14b[α]22 D-16.9° (c 1.0, MeOH) 1H NMR 300 MHz, CDCl3) δ 7.18 & 7.12 (2H, two d), 6.85 (2H,d), 4,58 (1H, two t), 3.80 (3H, s), 3.24 & 3.13 (1H, 2dd), 2.76 & 2.68 (3H, 2s), 1.43 & 1.38 (9H, 2s); FABMS 619.3 (2M+H), 310.2 (M+H), 210.2 (M−Boc); HRFABMS Calcd for C16H24MO5 (M+H) 310.1654, Found 310.1648.

Workup

  1. customat rt
  2. customovernight
  3. customExcess sodium hydride was quenched by the dropwise addition of 10 mL of THF/H2O (1:1)
  4. customthe solvents were removed in vacuo
  5. customAfter removal of the solvents
  6. additionthe deep orange gel was diluted with 30 mL of water
  7. washwashed with pentane (2×30 mL)
  8. extractionEthyl acetate was used for extraction
  9. washThe combined extracts were washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customThe crude residue was purified by silica gel column chromatography
  13. washeluting with ethyl ether

Sources & evidence

ORD record
ord-21b04f5c7ff243cb9583f7582d0d587d
Source dataset
uspto-grants-2002_04
Patent number
US06380156B1

Reaction notes

Loading…