1,2-Dichloroethane → N-(2,6-Dimethoxybenzoyl)-(O-benzyl)-L-tyrosine Methyl Ester

HRID 1267970Notes

Reaction equation

HRID 1267970 reaction equation
C(Cl)CCl.Cl.[CH3:6][O:7][C:8](=[O:26])[C@H:9]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:14][CH:13]=1)[NH2:10].[CH3:27][O:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[C:30]=1[C:31](O)=[O:32].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>C(Cl)Cl>[CH3:6][O:7][C:8](=[O:26])[C@H:9]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[CH:14][CH:13]=1)[NH:10][C:31](=[O:32])[C:30]1[C:34]([O:38][CH3:39])=[CH:35][CH:36]=[CH:37][C:29]=1[O:28][CH3:27]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 151092,6-Dimethoxybenzoic AcidHCID 757711-HydroxybenzotriazoleHCID 12616037H-Tyr(Bzl)-OMe.HCl

Product 1

HCID 54099706N-(2,6-Dimethoxybenzoyl)-(O-benzyl)-L-tyrosine Methyl EsterYield 87.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

EDC (212 mg, 1.1 mmol) was added to a solution of (O-benzyl)tyrosine methyl ester hydrochloride (322 mg, 1 mmol), 2,6-dimethoxybenzoic acid (182 mg, 1 mmol), HOBT (149 mg, 1.1 mmol) and NMM (242 μl, 2.2 mmol) in DCM (10 ml). The mixture was stirred at room temperature overnight, then diluted with DCM (100 ml), washed with 10% citric acid (20 ml), saturated sodium bicarbonate solution (20 ml) and brine (20 ml), dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by column chromatography (SiO2; EtOAc/hexane, 60:40) to give the title compound as a colourless gum (392 mg, 87%). δH (CDCl3) 7.44-7.31 (5H, m, OCH2Ph), 7.29 (1H, t, 18.4 Hz, Ar(OMe)H), 7.14 (2H, d, 18.7 Hz, CH2Ar(O)H), 6.88 (2H, d, J 8.7 Hz, CH2Ar(O)H), 6.55 (2H, d, J 8.4 Hz, Ar(OMe)H), 6.36 (1H, br d, 17.4 Hz, CONH), 5.11 (1H, dt, J 7.5, 5.2 Hz, CHαtyr) 5.02 (2H, s, OCH2Ph), 3.80 (6H, s, 2×ArOMe), 3.72 (3H, s, CO2Me), 3.29 (1H, dd, J 5.5, 14.0 Hz. CHCHAHBAr) and 3.16 (1H, dd, J 4.9, 14.0 Hz, CHCHAHBAr); m/z (ESI, 15V) 450 (Mh+).

Workup

  1. washwashed with 10% citric acid (20 ml), saturated sodium bicarbonate solution (20 ml) and brine (20 ml)
  2. dry with materialdried (Na2SO4)
  3. customevaporated under reduced pressure
  4. customThe residue was purified by column chromatography (SiO2; EtOAc/hexane, 60:40)

Sources & evidence

ORD record
ord-54c6a46764284b42a4bd519d9a1f6933
Source dataset
uspto-grants-2003_04
Patent number
US06555562B1

Reaction notes

Loading…