Reaction #83122

Reaction equation

α-methyl-D-tryptophyl-L-phenylalaninol

2-adamantylchloroformate

→

required compound

Tricyclo[3.3,1.13,7 ]dec-2-yl-[2-[[1-(hydroxymethyl)-2-phenylethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamate

carbonate

Yield 20.0%

Solvents

THF

THF

ethyl acetate

Conditions

Workup

1. 1
   Washwashed with 1M citric acid solution
2. 2
   DryingThe dried (MgSO4) organic phase
3. 3
   Otherwas evaporated to dryness
4. 4
   Otherchromatographed over silica using 2% MeOH

Procedure

A solution of the α-methyl-D-tryptophyl-L-phenylalaninol (0.5 g, 1.42 mmol) and 4-N,N-dimethylaminopyridine (0.2 g, 1.64 mmol), in anhydrous THF (20 mL) was treated dropwise with a solution of 2-adamantylchloroformate (1.4 mmol) in anhydrous THF (20 mL) at room temperature. The reaction was monitored by IR spectroscopy. Once complete, the reaction mixture was diluted with ethyl acetate and washed with 1M citric acid solution, then water. The dried (MgSO4) organic phase was evaporated to dryness and chromatographed over silica using 2% MeOH:98% CH2Cl2 as eluant. This gave the required compound (65% along with 20% carbonate impurity. NOTE: Some of the more acid labile urethanes required chromatography on neutral stationary phases. mp 96°-100° C. (EtOAc-hexane); IR (KBr) 3316, 1695 and 1658 cm-1 ; NMR (CD3OD) δ1.28 (3H, s), 1.55 (2H, m), 1.68-2.06 (12H, m), 2.76 (2H, ABx, J 13.5 and 17Hz), 3.31 (2H, Abq, J 14.5Hz), 3.45 (2H, m), 4.12 (1H, m), 4.78 (1H, br.s) and 6.8-7.5 (10H, m); Anal (C32H39N3O4), C, H, N.

Source