Hydrochloric Acid → HCID 86695421, compound

HRID 1487463Notes

Reaction equation

HRID 1487463 reaction equation
[F:1][CH:2]([F:27])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[S:22][C:21]([CH2:23]O)=[N:20][CH:19]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:26])[CH3:25])=[O:4].[N:28]1C=CC=C[CH:29]=1.C(N(C(C)C)CC)(C)C.CN.Cl>C(Cl)Cl.C([O-])(O)=O.[Na+]>[F:1][CH:2]([F:27])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[S:22][C:21]([CH2:23][NH:28][CH3:29])=[N:20][CH:19]=3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:25])[CH3:26])=[O:4]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 86695419HCID 86695419, compound

Product 1

HCID 86695421HCID 86695421, compoundYield 32.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Mesyl anhydride (860 mg, 4.9 mmol) is added to 2,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-5-(4-(2-(hydroxymethyl)thiazol-5-yl)phenyl)-2,2-dimethyl-oxazolidin-3-yl)ethanone (1.4 g, 3.5 mmol) in CH2Cl2 (35 mL). Pyridine (0.5 mL, 5.9 mmol) is added and stirred at room temperature for 1 hour. The reaction is diluted with CH2Cl2 (35 mL) and washed with water and brine. The organic phase is dried (Na2SO4) and concentrated under vacuum. The crude mesylate is dissolved in acetonitrile (10 mL) and transferred to a scintillation vial. Diisopropylethylamine (0.65 mL, 3.7 mmol) and methylamine.HCl (130 mg, 1.9 mmol) are added and the reaction mixture is heated to 55° C. for 18 hours. The reaction mixture is cooled and diluted with saturated NaHCO3 (75 mL). The reaction mixture is extracted with CH2Cl2 (2×75 mL) and the combined organic phase is dried (Na2SO4) and concentrated under vacuum to afford the title compound (475 mg): m/z (CI) M+H 414.

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic phase is dried (Na2SO4)
  3. concentrationconcentrated under vacuum
  4. dissolutionThe crude mesylate is dissolved in acetonitrile (10 mL)
  5. temperaturethe reaction mixture is heated to 55° C. for 18 hours
  6. temperatureThe reaction mixture is cooled
  7. extractionThe reaction mixture is extracted with CH2Cl2 (2×75 mL)
  8. dry with materialthe combined organic phase is dried (Na2SO4)
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-41a3de86776b4b71a0a7effc1ef8e5d6
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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