Water → N-Boc-O-isopropyl-L-tyrosine

HRID 1589317Notes

Reaction equation

HRID 1589317 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH:24]([CH3:26])[CH3:25].O>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:18]([OH:20])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH:24]([CH3:26])[CH3:25])=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 63582-BromopropaneHCID 24758Sodium hydrideHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-

Product 1

HCID 18601565N-Boc-O-isopropyl-L-tyrosineYield 84.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

N-Tertiarybutyloxycarbonyl-L-tyrosine (14.1 g 50 mM) in dry dimethylformamide (200 ml) was treated with sodium hydride (3.45 g, 115 mM) with vigorous stirring under an atmosphere of argon at 10° C. for 1 h. 2-Bromopropane (6.15 g, 50 mM) was added and the stirred solution allowed to warm to 20° C. over 16 h. Water (200 ml) was added and the solution extracted with ethyl acetate (2×200 ml). The reaction was adjusted to pH1 with hydrochloric acid (6M) and extracted with dichloromethane 2×300 ml. The combined extracts were columned on silica in ethyl acetate to afford N-tertiarybutyloxycarbonyl-O-isopropyl-L-tyrosine (13.6 g, 42 mM) as a foam. The foam was dissolved in dichloromethane (200 ml) and treated with methylamine hydrochloride (2.5 g, 80 mM), 1-hydroxybenzotriazole (6.75 g, 44 mM), dicyclohexylcarbodiimide (9.1 g, 44 mM) and N-methyl morpholine (2.5 g, 80 mM) at 0° C. with continuous stirring. The solution was allowed to warm to room temperature over 16 h and filtered. The filtrate was washed with water, aqueous saturated sodium hydrogen carbonate solution and aqueous citric acid (1M), dried over sodium sulphate and concentrated in vacuo to afford N-tertiarybutyloxycarbonyl-O-isopropyl-L-tyrosine-N-methyl amide (6.1 g, 18 mM) which crystallised from ethyl acetate/hexane as needles m.p. 110°-114° C. (Found: C,63.5; H,8.4; N,8.7. C18H28N2O4 0.25 H2O requires: C,63.4; H,8.4; N,8.2%) δ(CDCl3) 1.32 (6H,d,J=7 Hz, (CH3)2CH); 1.4 (9H,s,(CH3)3C); 2.72 (3H,d,J=4 Hz NHCH3); 2.98, (2H,d,J=7 Hz CH2C6H5); 4.26 (1H,m,NHCHCO); 4.5 (1H, heptet, J=5 Hz, CH(CH3)2); 5.08 (1H,m,NH); 5.92 (1H,m,NH); 6.78, and 7.04 (each 2H,each d,each J=8 Hz C6H4).

Workup

  1. temperatureto warm to 20° C. over 16 h
  2. extractionthe solution extracted with ethyl acetate (2×200 ml)
  3. extractionextracted with dichloromethane 2×300 ml

Sources & evidence

ORD record
ord-25c0181a4625436b996c7913b1d46277
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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