Acetyl chloride → HCID 59223144, compound

HRID 539143Notes

Reaction equation

HRID 539143 reaction equation
[CH2:1]([C@H:8]1[NH:23][C:22](=[O:24])[C@@H:21]([CH3:25])[NH:20][C:19](=[O:26])[CH2:18][C@@H:17](/[CH:27]=[CH:28]/[CH2:29][CH2:30][S:31][C:32](C2C=CC=CC=2)([C:39]2C=CC=CC=2)C2C=CC=CC=2)[O:16][C:15](=[O:51])[CH2:14][NH:13][C:12](=[O:52])[C@@H:11]([CH:53]([CH3:55])[CH3:54])[NH:10][C:9]1=[O:56])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=[O:65].C([C@H]1NC(=O)[C@@H](C)NC(=O)C[C@@H](/C=C/CCS)OC(=O)CNC(=O)[C@@H](C(C)C)NC1=O)C1C=CC=CC=1.CCN(C(C)C)C(C)C.C(Cl)(C)=O>C(Cl)Cl>[CH2:1]([C@H:8]1[NH:23][C:22](=[O:24])[C@@H:21]([CH3:25])[NH:20][C:19](=[O:26])[CH2:18][C@@H:17](/[CH:27]=[CH:28]/[CH2:29][CH2:30][S:31][C:32](=[O:65])[CH3:39])[O:16][C:15](=[O:51])[CH2:14][NH:13][C:12](=[O:52])[C@@H:11]([CH:53]([CH3:54])[CH3:55])[NH:10][C:9]1=[O:56])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 6367Acetyl chlorideHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 81531DiisopropylethylamineHCID 59223146HCID 59223146, compoundHCID 59223148HCID 59223148, compound

Product 1

HCID 59223144HCID 59223144, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 15 (15 mg, 19 μmol) in CH2Cl2 (0.8 mL) was added Et3SiH (16 μL, 0.1 mmol) and TFA (0.2 mL). After stirring at room temperature for 30 minutes under an inert atmosphere, the reaction mixture was concentrated and the residue dried by high vacuum. Without further purification, the crude thiol 16 was used in next step. At 0° C., to a stirred solution of thiol 16 in CH2Cl2 (0.3 mL) was added DIPEA (17 μL, 0.1 mmol) and AcCl (2 μL, 28 □mol). After 30 minutes the reaction mixture was warmed to rt and stirred for a further 1.5 h, whereupon it was quenched by addition of 1M HCl (1 mL). EtOAc (5 mL) was added to dilute the solution, phases separated, and the aqueous phase extracted with EtOAc (2×1 mL). The combined organic phases were washed with sat. aq NaCl (2 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (eluent: 1-10% IPA/CH2Cl2) to give compound 17 (5 mg, 8 μmol, 45%) as an off white solid.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe residue dried by high vacuum
  3. customWithout further purification
  4. temperatureAfter 30 minutes the reaction mixture was warmed to rt
  5. stirringstirred for a further 1.5 h, whereupon it
  6. customwas quenched by addition of 1M HCl (1 mL)
  7. additionEtOAc (5 mL) was added
  8. additionto dilute the solution, phases
  9. customseparated
  10. extractionthe aqueous phase extracted with EtOAc (2×1 mL)
  11. washThe combined organic phases were washed with sat. aq NaCl (2 mL)
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by flash chromatography (eluent: 1-10% IPA/CH2Cl2)

Sources & evidence

ORD record
ord-8cb1f094d47a49079105df77df0976a7
Source dataset
uspto-grants-2014_10
Patent number
US08865655B2

Reaction notes

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