Dimethylformamide → HCID 69331356, compound

HRID 1264975Notes

Reaction equation

HRID 1264975 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17](O)=[CH:16][CH:15]=1)[NH:5]C(OC(C)(C)C)=O.C(=O)([O-])[O-].[K+].[K+].[CH3:28][OH:29].C(Cl)Cl.[CH3:33][N:34]([CH:36]=O)C>>[C:28]1([O:29][C:17]2[CH:16]=[CH:15][C:14]([CH2:13][C@H:4]([NH2:5])[C:3]([O:2][CH3:1])=[O:21])=[CH:19][CH:18]=2)[C:19]2[C:14](=[CH:15][CH:33]=[N:34][CH:36]=2)[CH:13]=[CH:4][N:5]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 7019130Boc-Tyr-OMeHCID 21226129Dichloromethane methanol

Product 1

HCID 69331356HCID 69331356, compoundYield 71%

Procedure

A mixture of N-(BOC)-(S)-tyrosine methyl ester (1.71 g, 5.80 (mmol) potassium carbonate (0.80 g, 5.80 mmol) and Intermediate 3 (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 colorless oil. Chromatography (silica; 2.5% MeOH/DCM) afforded reasonably pure N-t-butoxycarbonyl protected title compound (1.75 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 (2×20ml). 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 colorless oil (0.83 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 (1H, d, J 5.9 Hz), 7.21 (2H, d, J 8.4 Hz), 3.80-3.70 (1H, obscured m), 3.72 (3H, s), 3.15 (1H, dd, J 13.6, 5.1 Hz), 2.88 (1H, dd, J 13.6, 8.0 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 colorless oil

Sources & evidence

ORD record
ord-5daf21ffa3284d579da901e2bf0a6efd
Source dataset
uspto-grants-2003_04
Patent number
US06545013B2

Reaction notes

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