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

HRID 1921

Reaction equation

HRID 1921 reaction equation
O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:15][NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:5][CH:4]=1.CS(Cl)(=O)=O.[CH2:29]([N:31](CC)CC)[CH3:30].C(N)C>C(Cl)Cl.CO.C(OCC)(=O)C>[CH2:29]([NH:31][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH2:15][NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:5][CH:4]=1)[CH3:30]

Participants

8

Reactant 4

HCID 6341EthylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 220084722'-[(t-Butoxycarbonylamino)methyl]-1,1-biphenyl-4-methanol

Product 1

HCID 196929074-[N-Ethyl-(aminomethyl)]-2'(t-butoxycarbonylaminomethyl)-1,1'-biphenylYield 68.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
0 °C

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).

Workup

  1. stirringThe reaction mixture was stirred for 3 h at 0° C.
  2. stirringThe mixture was stirred for 5 h at room temperature vigorously
  3. custompartitioned between water and methylene chloride
  4. customThe organic phase was separated
  5. extractionthe aqueous layer extracted with methylene chloride (2×25 ml)
  6. dry with materialThe combined methylene chloride layers were dried over potassium carbonate powder
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto leave a thick viscous oil

Sources & evidence

ORD record
ord-31a415ff907141efa27a3abe2528614f
Source dataset
uspto-grants-1998_03
Patent number
US05726319

Linked notes

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