Pyridine → HCID 14824298, compound

HRID 1354404Notes

Reaction equation

HRID 1354404 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([OH:18])=O)[CH:13]([CH3:15])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.N1C(F)=NC(F)=NC=1[F:27].C(Cl)(Cl)Cl.CO.CC(O)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:16]([F:27])=[O:18])[CH:13]([CH3:15])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 12664Cyanuric fluorideHCID 726987N-Carbobenzoxy-L-valineHCID 21866353chloroform methanol HOAc

Product 1

HCID 14824298HCID 14824298, compoundYield 119%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-benzyloxycarbonyl-L-valine (0.50 g, 2.00 mmol) and pyridine (0.16 ml, 2.00 mmol) in anhydrous DCM (5 ml) kept under a N2 atmosphere was added cyanuric fluoride (0.90 ml, 10.00 mmol) at −15 to −10° C. A white precipitate formed. The reaction was followed by TLC CHCl3/MeOH/AcOH (9:1:0.1) on a small amount of reaction mixture quenched in MeOH. After 1 hr 40 min, crushed ice was added along with DCM (10 ml). The organic layer was separated and the aqueous layer extracted with DCM (5 ml). The combined DCM layers were washed with ice-cold water (10 ml), dried (MgSO4) and concentrated under reduced pressure to afford a colourless oil (0.60 g, 119%) which was used in subsequent reactions without further purification: Rf=0.78 CHCl3/MeOH/AcOH (9:1:0.1); νmax(polyethylene card) 3320 (N—H), 1843 (acid fluoride), 1738 (urethane, C═O), 1538 (amide II); δH (200 MHz, CDCl3) 1.01 (3H, d, J 7.0, CH(CAH3CBH3)), 1.05 (3H, d, J 7.0, CH(CAH3CBH3)), 2.26 (1H, m, CH(CH3)2), 4.49 (1H, m, NHCH), 5.14 (3H, m, OCH2Ph & NH (masked)), 7.37 (5H, s, Ar—H); MS ES (+ve) found m/z 233.8 (C6H5CH2CONHCH(CH(CH3)2)CO—, 41%), 251.8 (N-Cbz-Val, 58), 268.9 (N-Cbz-ValNH4+, 64), 273.8 (N-Cbz-ValNa+, 33), 289.9 (N-Cbz-ValK+, 22), 341.9 (100), 502.1 (N-Cbz-Val dimer, 53), 507.1 (M+ dimer, 55).

Workup

  1. customA white precipitate formed
  2. customquenched in MeOH
  3. customcrushed ice
  4. additionwas added along with DCM (10 ml)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer extracted with DCM (5 ml)
  7. washThe combined DCM layers were washed with ice-cold water (10 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cdab213018a745e6a22bbc4956fe607c
Source dataset
uspto-grants-2007_05
Patent number
US07223795B2

Reaction notes

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