Methylamine → N-(Benzyloxycarbonyl)-O-methyl-L-tyrosine N-Methylamide

HRID 1980832Notes

Reaction equation

HRID 1980832 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:22]([OH:24])=O)[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[N:26]1[C:30]2C=CC=CC=2N=N1.C1CCC(N=C=NC2CCCCC2)CC1.CN>C(Cl)Cl>[CH3:30][NH:26][C:22](=[O:24])[C@H:12]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 10496574(2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-methoxyphenyl)propanoic acid

Product 1

HCID 53688629N-(Benzyloxycarbonyl)-O-methyl-L-tyrosine N-MethylamideYield 88.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a stirred solution of N-(Benzyloxycarbonyl)-O-methyl-L-tyrosine (155 g, 0.471M) in dry CH2Cl2 was added 1-hydroxybenzotriazole (63.6 g, 0.471M) followed by a solution of DCC (97.2 g, 0.0471M) in CH2Cl2 (100 ml) added slowly at 0° C. After warming to room temperature over 1 hr, a solution of methylamine (30 g) in CH2Cl2 (250 ml) was added dropwise to the reaction mixture which was then stirred overnight at room temperature. The reaction was then filtered, washed with saturated aqueous sodium bicarbonate (x2), dried (MgSO4) and concentrated in vacuo to give a solid. Recrystallisation from ethyl acetate/hexane gave the desired amide (142 g); m.p. 167°-170°; (Found: C,66.72; H,6.58; N,8.29. C19H22N2O4 requires C,66.65; H,6.48; N,8.18%)νmax (CHCl3) 3440, 1710 and 1672 cm-1 ; δ (CDCl3) 2.70 (3H,d,J=5 Hz,NCH3); 2.98 (2H,m,CH2C6H4); 3.77 (3H,s,OCH3); 4.30 (1H,dd,J=7.6 and 3 Hz, α--CH); 5.06 (2H,m,OCH2C6H5); 5.43 (1H,m,OCONH); 5.84 (1H,m,CONH); 6.80 (2H,d,J=8.6 Hz, Tyr H-3 and H-5); 7.15 (2H,d,J=8.6 Hz, Tyr H-2 and H-6); 7.32 (5H,m,C6H5); m/e 343 (100%, [m+1]+).

Workup

  1. additionadded slowly at 0° C
  2. filtrationThe reaction was then filtered
  3. washwashed with saturated aqueous sodium bicarbonate (x2)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give a solid
  7. customRecrystallisation from ethyl acetate/hexane

Sources & evidence

ORD record
ord-7ae77098e7eb41418ff0bc1b7f4ff8e5
Source dataset
uspto-grants-1985_04
Patent number
US04511504

Reaction notes

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