Thioglycolic Acid → HCID 67272425, compound

HRID 1698377Notes

Reaction equation

HRID 1698377 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([NH:14]S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH2:11][C@@H:10]([C:27](=[O:50])[N:28]([CH:47]2[CH2:49][CH2:48]2)[C:29]2[CH:30]=[CH:31][C:32]3[O:37][C:36]([CH3:39])([CH3:38])[C:35](=[O:40])[N:34]([CH2:41][CH2:42][CH2:43][O:44][CH3:45])[C:33]=3[CH:46]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].IC.[C:53]([O-])([O-])=O.[K+].[K+].C(O)(=O)CS.[Li+].[OH-]>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([NH:14][CH3:53])[CH2:11][C@@H:10]([C:27](=[O:50])[N:28]([CH:47]2[CH2:49][CH2:48]2)[C:29]2[CH:30]=[CH:31][C:32]3[O:37][C:36]([CH3:38])([CH3:39])[C:35](=[O:40])[N:34]([CH2:41][CH2:42][CH2:43][O:44][CH3:45])[C:33]=3[CH:46]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 1133Thioglycolic AcidHCID 3939Lithium HydroxideHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 67273759HCID 67273759, compound

Product 1

HCID 67272425HCID 67272425, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (3R,5S)-3-{Cyclopropyl-[4-(3-methoxy-propyl)-2,2-dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl]-carbamoyl}-5-(2-nitro-benzenesulfonylamino)-piperidine-1-carboxylic acid tert-butyl ester (550 mg, 0.78 mmol) in DMF (5 mL), iodomethane (81 μL, 0.94 mmol) and K2CO3 (320 mg, 2.3 mmol) are added at rt. After stirring overnight, the reaction mixture is diluted with H2O and extracted with EtOAc. The combined organic phases are washed with H2O and dried over Na2SO4. Concentration under reduced pressure and filtration through silica gel give crude product. To a solution of the crude product in DMF (3 mL), thioglycolic acid (160 μL, 2.3 mmol) and LiOH (93 mg, 3.9 mmol) are added at rt. After stirring for 4 hours, the reaction mixture is diluted with H2O and extracted with EtOAc. The combined organic phases are washed with H2O and dried over Na2SO4. Concentration under reduced pressure and filtration through silica gel give the title compound. MS: 545 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 3.05 min.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic phases are washed with H2O
  3. dry with materialdried over Na2SO4
  4. concentrationConcentration
  5. filtrationunder reduced pressure and filtration through silica gel
  6. customgive crude product
  7. stirringAfter stirring for 4 hours
  8. extractionextracted with EtOAc
  9. washThe combined organic phases are washed with H2O
  10. dry with materialdried over Na2SO4
  11. concentrationConcentration
  12. filtrationunder reduced pressure and filtration through silica gel

Sources & evidence

ORD record
ord-2a51881fb88f44528bf823564f9f6fb4
Source dataset
uspto-grants-2012_04
Patent number
US08163773B2

Reaction notes

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