Dichloromethane → HCID 57504937, compound

HRID 2060803Notes

Reaction equation

HRID 2060803 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)=[CH:4][C:3]=1[C:15]12[CH2:24][CH2:23][O:22][CH2:21][CH:20]1[CH2:19][S:18][C:17]([NH:25]C(=O)OC(C)(C)C)=[N:16]2.C(O)(C(F)(F)F)=O.C(Cl)[Cl:41]>O.[OH-].[Na+]>[ClH:41].[ClH:41].[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:9]2[CH:10]=[N:11][CH:12]=[N:13][CH:14]=2)=[CH:4][C:3]=1[C@:15]12[CH2:24][CH2:23][O:22][CH2:21][CH:20]1[CH2:19][S:18][C:17]([NH2:25])=[N:16]2

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 57504939HCID 57504939, compound

Product 1

HCID 57504937HCID 57504937, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of tert-butyl 8a-(2,4-difluoro-5-(pyrimidin-5-yl)phenyl)-4,4a,5,7,8,8a-hexahydropyrano[4,3-d][1,3]thiazin-2-ylcarbamate (0.258 g, 0.558 mmol) in CH2Cl2 (8 mL) is added TFA (4 mL) and the reaction is stirred at room temperature for 1 hour. The solvent is removed under reduced pressure to afford a residue that is diluted with water and 1 N NaOH to adjust the pH to 12. The aqueous layer is extracted three times with EtOAc. The organic layer is dried over Na2SO4 and the crude product is purified by silica gel chromatography eluting with a linear gradient of 1% to 10% 7 N NH3/MeOH in CH2Cl2 to afford the title compound as the freebase (0.165 g, 68%). The freebase (0.162 g, 0.448 mmol) is dissolved in CH2Cl2 and treated with of 1 M HCl in Et2O (0.94 mL, 0.940 mmol) and the solvent is removed under reduced pressure to afford the title compound (0.208 g, 86%). ES/MS m/e: 363 (M+1).

Workup

  1. customThe solvent is removed under reduced pressure
  2. customto afford a residue that
  3. extractionThe aqueous layer is extracted three times with EtOAc
  4. dry with materialThe organic layer is dried over Na2SO4
  5. customthe crude product is purified by silica gel chromatography
  6. washeluting with a linear gradient of 1% to 10% 7 N NH3/MeOH in CH2Cl2

Sources & evidence

ORD record
ord-191ebf38d78b4441a4a20e7037fd8bce
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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