Reaction #2017

Reaction equation

methanesulfonyl chloride

triethylamine

ethylamine

4-Hydroxymethyl-2'(t-butoxycarbonylaminomethyl)-1,1'-biphenyl

→

desired product

Yield 68.2%

4-[N-Ethyl-(aminomethyl)]-2'(t-butoxycarbonylaminomethyl)-1,1'-biphenyl

Yield 68.2%

Solvents

ethyl acetate

—

hexanes

methanol

ethyl acetate

ethyl acetate

methylene chloride

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture was stirred for 3 h at 0° C.
2. 2
   workup.STIRRINGThe mixture was stirred for 5 h at room temperature vigorously
3. 3
   Otherpartitioned between water and methylene chloride
4. 4
   OtherThe organic phase was separated
5. 5
   Extractionthe aqueous layer extracted with methylene chloride (2×25 ml)
6. 6
   DryingThe combined methylene chloride layers were dried over potassium carbonate powder
7. 7
   Filtrationfiltered
8. 8
   Otherevaporated under reduced pressure
9. 9
   Otherto leave a thick viscous oil

Procedure

4-Hydroxymethyl-2'(t-butoxycarbonylaminomethyl)-1,1'-biphenyl (70 mg; 0.224 mmol) was dissolved in dry methylene chloride and stirred at 0° C. in an iced water bath and methanesulfonyl chloride (22 μl; 0.285 mmol) and triethylamine (39 μl; 0.280 mmol) added. The reaction mixture was stirred for 3 h at 0° C. and then 70% aqueous ethylamine (5 ml) added. The mixture was stirred for 5 h at room temperature vigorously, then partitioned between water and methylene chloride. The organic phase was separated and the aqueous layer extracted with methylene chloride (2×25 ml). The combined methylene chloride layers were dried over potassium carbonate powder, filtered and evaporated under reduced pressure to leave a thick viscous oil. The oil was subjected to a short column chromatography using a solvent gradient initially of ethyl acetate and hexanes (1:1 v/v) then neat ethyl acetate and finally with ethyl acetate and methanol (3:1 v/v). This afforded 52 mg (68%) of the desired product. FAB-MS:- calculated for C21H28N2O2 340.2 found 341.1 (M+1).

Source