4-Methylmorpholine → N-Boc-O-benzyl tyrosine methylamide

HRID 1589320Notes

Reaction equation

HRID 1589320 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([OH:27])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:29]1[C:33]2C=CC=CC=2N=N1.Cl.CN.CN1CCOCC1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[CH3:33][NH:29][C:25](=[O:27])[C@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][CH:12]=1)[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 98763O-benzyl-N-((tert-butoxy)carbonyl)-L-tyrosineHCID 6364545Methylamine hydrochloride

Product 1

HCID 14505564N-Boc-O-benzyl tyrosine methylamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-tertiarybutoxycarbonyl-O-benzyl-L-tyrosine (7.4 g, 20 mM), 1-hydroxybenzotriazole (3 g, 20 mM), methylamine HCl (1.3 g, 20 mM) and N-methylmorpholine (2 g, 20 mM) in CH2Cl2 (20 ml) stired and cooled to 0° was added DCC (4.2 g, 20 mM). After being allowed to stir and warm to room temperature overnight the reaction mixture was filtered and washed with saturated aqueous sodium bicarbonate solution, 3N citric acid and brine. The dried organic extract was then concentrated in vacuo to give N-tertiarybutoxycarbonyl-O-benzyl-L-tyrosine N-methylamide as a solid. Recrystallisation from dichloromethane/hexane gave (4.5 g); m.p. 165°-172°; (Found: C, 68.85; H, 7.43; N, 7.39. C22H28N2O4 requires C, 68.73; H, 7.34; N, 7.29%); δ (CDCl3) 1.40 (9H, s, OC(CH3)3); 2.73 (3H, d, J=5 Hz, CONHCH3); 2.96 (2H, m, CH2Tyr); 4.25 (1H, m, α-CH); 5.03 (2H, s, CH2C6H5); 5.80 (1H, br, CONH); 6.86 (2H, d, J=8 Hz, Tyr); 7.12 (2H, d, J=8 Hz, Tyr); 7.3-7.5 (5H, m, C6H5).

Workup

  1. temperaturecooled to 0°
  2. filtrationwas filtered
  3. washwashed with saturated aqueous sodium bicarbonate solution, 3N citric acid and brine
  4. extractionThe dried organic extract
  5. concentrationwas then concentrated in vacuo

Sources & evidence

ORD record
ord-6547b199b72a49a6bfdecb5095a5558d
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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