Ethanol → HCID 18601572, compound

HRID 1589318Notes

Reaction equation

HRID 1589318 reaction equation
[CH3:1][NH:2][C:3](=[O:28])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:19][CH:18]=1)[NH:5]C(OCC1C=CC=CC=1)=O.C1CCCCC=1.C([OH:37])C>[Pd]>[C:24]([OH:37])(=[O:23])[CH3:27].[CH3:1][NH:2][C:3](=[O:28])[C@H:4]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:21][CH:22]=1)[NH2:5]

Participants

5

Reactant 3

HCID 702EthanolHCID 8079CyclohexeneHCID 18601528HCID 18601528, compound

Product 1

HCID 18601572HCID 18601572, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

N-Benzyloxycarbonyl-O-tertiarybutyl-L-tyrosine N-methylamide (2.4 g 6.2 mM) in ethanol (10 ml) was heated under reflux with cyclo hexene (4 ml) acetic acid (0.38 g 6.2 mM) and palladium on carbon (10%, 1 g) under an atmosphere of argon for 20 m. The solvents were then removed in vacuo to afford O-tertiarybutyl-L-tyrosine N-methylamide acetate m.p. 121°-123° C. This was dissolved in dichloromethane (50 ml) and shaken with aqueous saturated sodium hydrogen carbonate (50 ml). The organic layer was dried over anhydrous sodium sulphate and concentrated in vacuo to afford O-tertiary butyl-L-tyrosine N-methyl amide as a crude gum which was used directly in the next step. N-[3-N-Benzyloxy carbonyl]amino-1-(R)-methoxycarbonylpropyl]-L-leucine hydrochloride (418 mg, 1 mM) in dichloromethane (10 ml) was treated with 1-hydroxybenzotriazole (159 mg, 1.0 mM) N-methylmorpholine (210 mg, 2 mM), O-tertiarybutyl-L-tyrosine-N-methyl amide (275 mg, 1.1 mM) and N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide hydrochloride (200 mg, 1.04 mM) at 0° C. with continuous stirring. The reaction mixture was adjusted to pH7 with N-methylmorpholine and was allowed to warm to 20° C. over 16 h. The reaction was diluted with dichloromethane and washed successively with water, aqueous saturated sodium hydrogen carbonate and aqueous 3N citric acid, dried over sodium sulphate and concentrated in vacuo to afford N-[3-N-(Benzyloxycarbonyl)amino-1-(R)-methoxy carbonypropyl]-L-leucine-O-tertiary butyl-L-tyrosine-N-methyl amide (350 mg, 0.6 mM) which crystallised from ethyl acetate/hexane as needles m.p. 66°-68° C. (Found: C,64.7; H,8.1; N,9.2. C33H48N4O7 requires: C,4.7; H,7.9; N,9.1%); δ(CDCl3) 0.88 (6H,d,J=7 Hz, (CH3)2C); 1.32 (9H,s, (CH3)3C); 1.16-2.0 (5H,m,CH2,CH2CH); 2.72 (3H,d,J=5 Hz, CH3NH); 3.02 to 3.4 (6H,m,2×CH,2×CH2); 3.66 (3H,s,CH3O); 4.58 (1H,m,NHCHCO); 5.08 (2H,s,CH2C5H6); 5.2 (1H,m,NH); 6.54 (1H,m,NH); 6.88 and 7.06 (each 2H,each d,each J=8 Hz,C6H4); 7.32 (5H,m,C6H5); 7.52 (1H,m,NH).

Workup

  1. customThe solvents were then removed in vacuo

Sources & evidence

ORD record
ord-2942541c247346c8beb88768740404dd
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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