Formic Acid → HCID 23001818, compound

HRID 398083Notes

Reaction equation

HRID 398083 reaction equation
[CH:1]1(N=C=NC2CCCCC2)CCCCC1.FC1C(O)=C(F)C(F)=C(F)C=1F.C(O)=O.[NH2:31][CH2:32][C:33]1[CH:34]=[C:35]([NH:50][S:51]([CH3:54])(=[O:53])=[O:52])[CH:36]=[CH:37][C:38]=1[O:39][C:40]1[CH:41]=[CH:42][C:43]2[O:48][CH2:47][CH2:46][S:45][C:44]=2[CH:49]=1.B.C1COCC1.C1COCC1.Cl>CCOCC.C(Cl)Cl.CCOC(C)=O>[O:48]1[C:43]2[CH:42]=[CH:41][C:40]([O:39][C:38]3[CH:37]=[CH:36][C:35]([NH:50][S:51]([CH3:54])(=[O:53])=[O:52])=[CH:34][C:33]=3[CH2:32][NH:31][CH3:1])=[CH:49][C:44]=2[S:45][CH2:46][CH2:47]1

Participants

11

Reactant 7

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 10868DicyclohexylcarbodiimideHCID 13041PentafluorophenolHCID 2723981Borane;tetrahydrofuranHCID 23001810HCID 23001810, compound

Product 1

HCID 23001818HCID 23001818, compoundYield 67.4%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dicyclohexylcarbodiimide (460 mg, 2.23 mmol) was added to a solution of pentafluorophenol (413 mg, 2.24 mmol) in ether (10 mL) followed by formic acid (95 μL, 2.5 mmol). The mixture was stirred for 2 h and then filtered, washing the residue with ether. The filtrate was concentrated to ˜5 mL and a solution of the primary amine of Example 105 (411 mg, 1.1 mmol) in DCM (10 mL) was added. The mixture was stirred for 16 h then concentrated to an oily residue. This crude oil was taken up in a solution of BH3.THF in THF (1M, 20 mL, 20 mmol) and heated at reflux for 1.5 h under N2. After cooling to room temperature the reaction was quenched by the cautious addition of MeOH (10 mL) and then concentrated in vacuo. The oily residue was treated with 6M HCl and heated at reflux for 30 min. After cooling to room temperature the mixture was basified with aq K2CO3 and extracted with DCM (3×). The combined organic extracts were dried (MgSO4) and evaporated. The residue was purified by column chromatography [SiO2; 90:10:1 (DCM/MeOH/880 NH3)] to give a colourless oil which was taken up in EtOAc (20 mL) and treated with 1M ethereal HCl (2 mL). After stirring for 1.5 h the solid was collected by filtration to give the title product (282 mg, 60%); δH (CD3OD, 400 MHz) 2.78 (3H, s), 2.98 (3H, s), 3.18 (2H, m), 4.29 (2H, s), 4.39 (2H, m), 6.74 (1H, d), 6.80-6.90 (3H, m), 7.22 (1H, d), 7.44 (1H, s); MS m/z (TS+) 381 (MH+).

Workup

  1. filtrationfiltered
  2. washwashing the residue with ether
  3. concentrationThe filtrate was concentrated to ˜5 mL
  4. stirringThe mixture was stirred for 16 h
  5. concentrationthen concentrated to an oily residue
  6. temperatureheated
  7. temperatureat reflux for 1.5 h under N2
  8. customwas quenched by the cautious addition of MeOH (10 mL)
  9. concentrationconcentrated in vacuo
  10. additionThe oily residue was treated with 6M HCl
  11. temperatureheated
  12. temperatureat reflux for 30 min
  13. temperatureAfter cooling to room temperature the mixture
  14. extractionextracted with DCM (3×)
  15. dry with materialThe combined organic extracts were dried (MgSO4)
  16. customevaporated
  17. customThe residue was purified by column chromatography [SiO2; 90:10:1 (DCM/MeOH/880 NH3)]
  18. customto give a colourless oil which
  19. stirringAfter stirring for 1.5 h the solid
  20. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-3238737784c54a788dfe125548e58657
Source dataset
uspto-grants-2003_08
Patent number
US06610747B2

Reaction notes

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