Dimethylformamide → Ethyl (s)-3-[4-(2,7-naphthyridin-1-yloxy)phenyl]-2-aminopropanoate

HRID 397467

Reaction equation

HRID 397467 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[C@H:5]([CH2:14][C:15]1[CH:20]=[CH:19][C:18](O)=[CH:17][CH:16]=1)[NH:6]C(OC(C)(C)C)=O)[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH3:29][OH:30].C(Cl)Cl.[CH3:34][N:35]([CH:37]=O)C>>[C:29]1([O:30][C:18]2[CH:17]=[CH:16][C:15]([CH2:14][C@H:5]([NH2:6])[C:4]([O:3][CH2:1][CH3:2])=[O:22])=[CH:20][CH:19]=2)[C:20]2[C:15](=[CH:16][CH:34]=[N:35][CH:37]=2)[CH:14]=[CH:5][N:6]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11077750Ethyl N-(tert-butoxycarbonyl)-L-tyrosinateHCID 21226129Dichloromethane methanol

Product 1

HCID 69375061Ethyl (s)-3-[4-(2,7-naphthyridin-1-yloxy)phenyl]-2-aminopropanoateYield 71%

Procedure

A mixture of N-(BOC)-(S)-tyrosine ethyl ester (1.79 g, 5.80 (mmol) potassium carbonate (0.80 g, 5.80 mmol) and Intermediate 12 (1.0 g, 6.08 mmol) in dry DMF (10 ml) was stirred at room temperature for 18 h, and at 40° for 18 h. The DMF was removed in vacuo and the residue partitioned between EtOAc (80 ml) and 10% aqueous Na2CO3 (20 ml). The phases were separated and the aqueous layer re-extracted with EtOAc (2×20 ml). The combined organic extracts were washed with brine (10 ml), dried (Na2SO4) and evaporated in vacuo to afford a new colourless oil. Chromatography (silica; 2.5% MeOH/DCM) afforded reasonably pure N-t-butoxycarbonyl protected title compound (1.81 g, 71%). This material was dissolved in EtOAc (40 ml) and HCl gas was bubbled through the stirred solution for 1 min. then the mixture was stirred for an additional 0.5 h. The volatiles were removed in vacuo affording a yellow solid which was partitioned between EtOAc (80 ml) and saturated aqueous NaHCO3 (20 ml). The phases were separated and the aqueous layer re-extracted with EtOAc (2×20 ml). The combined organic extracts were washed with brine (10 ml), dried (Na2SO4) and evaporated in vacuo. The obtained oil was chromatographed (silica; 5% MeOH/DCM) to afford the title compound as a near colourless oil (0.87 g, 62%) δH (CDCl3) 9.77 (1H, s), 8.75 (1H, d, J. 5.8 Hz), 8.10 (1H, d, J 5.8 Hz), 7.58 (1H, d, J 5.8 Hz), 7.29 (2H, d, J 8.4 Hz), 7.25 (1 H, d, J 5.9 Hz), 7.21 (2H, d, J 8.4 Hz), 4.22 (2H, q, J 7/1 Hz), 3.80-3.70 (1H, obscured m), 3.15 (1H, dd, J 13.6, 5.1 Hz), 2.88 (1H, dd, J 13.6, 8.0 Hz) 1.30 (3H, t, J 7.1 Hz) and 0.78 (2H, br s); m/z (ES+, 70V) 324 (MH+).

Workup

  1. waitat 40° for 18 h
  2. customThe DMF was removed in vacuo
  3. customthe residue partitioned between EtOAc (80 ml) and 10% aqueous Na2CO3 (20 ml)
  4. customThe phases were separated
  5. extractionthe aqueous layer re-extracted with EtOAc (2×20 ml)
  6. washThe combined organic extracts were washed with brine (10 ml)
  7. dry with materialdried (Na2SO4)
  8. customevaporated in vacuo
  9. customto afford a new colourless oil

Sources & evidence

ORD record
ord-4971910f60f14399999ab4ff30204ccd
Source dataset
uspto-grants-2003_08
Patent number
US06610700B2

Linked notes

Loading…