4-Bromophenol → HCID 59243605, compound

HRID 425019Notes

Reaction equation

HRID 425019 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.[CH:27]1([O:32][C:33](=[O:47])[C@@H:34]([NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:35][CH2:36][CH2:37]Br)[CH2:31][CH2:30][CH2:29][CH2:28]1.C([O-])([O-])=O.[Na+].[Na+].C(=O)([O-])[O-]>C(#N)C.ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:37][CH2:36][CH2:35][C@@H:34]([C:33]([O:32][CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31]2)=[O:47])[NH:39][C:40]([O:42][C:43]([CH3:45])([CH3:46])[CH3:44])=[O:41])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 78084-BromophenolHCID 10340Sodium CarbonateHCID 19660Carbonate IonHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 57699908HCID 57699908, compound

Product 1

HCID 59243605HCID 59243605, compoundYield 69.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-bromophenol (261 mg, 1.510 mmol) in acetonitrile (2 ml) under nitrogen, was added BEMP (397 μl, 1.373 mmol). The mixture was stirred at 50° C. for 30 minutes before being cooled to room temperature and (S)-5-bromo-2-tert-butoxycarbonylamino-pentanoic acid cyclopentyl ester (500 mg, 1.373 mmol) added as a solution in acetonitrile (2 ml). The reaction was heated at 50° C. for a further 1 hour and then the mixture was analysed by LCMS. The reaction was poured onto 2M Na2CO3 (100 ml) and extracted with EtOAc (2×100 ml). The combined organic layers were washed with 2M Na2CO3 (3×100 ml) and brine (100 ml), dried over magnesium sulphate, filtered and concentrated in vacuo to afford a colourless oil. MP-carbonate (1.0 g) was added to a solution of the crude product in dichloromethane (3.4 ml) and the solution was left overnight at room temperature. LCMS indicated complete removal of 4-bromophenol and so the reaction was filtered to remove the MP-carbonate and the resin was washed with DCM (2×50 ml). The filtrate was concentrated to afford the crude product which was purified by column chromatography eluting with 5% EtOAc in iso-hexane. Yield of title compound=435 mg, 0.953 mmol, 69.4% yield. m/z 456 and 458 [M+H]+.

Workup

  1. temperaturebefore being cooled to room temperature
  2. temperatureThe reaction was heated at 50° C. for a further 1 hour
  3. extractionextracted with EtOAc (2×100 ml)
  4. washThe combined organic layers were washed with 2M Na2CO3 (3×100 ml) and brine (100 ml)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a colourless oil
  9. waitthe solution was left overnight at room temperature
  10. customremoval of 4-bromophenol
  11. filtrationso the reaction was filtered
  12. customto remove the MP-carbonate
  13. washthe resin was washed with DCM (2×50 ml)
  14. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-da301dbade584d32926af255634a8b11
Source dataset
uspto-grants-2012_01
Patent number
US08106091B2

Reaction notes

Loading…