Lithium Hydroxide → HCID 86762246, compound

HRID 338155Notes

Reaction equation

HRID 338155 reaction equation
[F:1][C:2]1[S:6][C:5]([C@:7]23[CH2:15][N:14]([C:16]4[N:21]=[CH:20][CH:19]=[CH:18][N:17]=4)[CH2:13][C@H:12]2[CH2:11][S:10][C:9]([NH:22]C(=O)C2C=CC=CC=2)=[N:8]3)=[CH:4][CH:3]=1.[OH-].[Li+]>CO>[F:1][C:2]1[S:6][C:5]([C@:7]23[CH2:15][N:14]([C:16]4[N:17]=[CH:18][CH:19]=[CH:20][N:21]=4)[CH2:13][C@H:12]2[CH2:11][S:10][C:9]([NH2:22])=[N:8]3)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86762247HCID 86762247, compound

Product 1

HCID 86762246HCID 86762246, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To N-[(4aR,7aR)-7a-(5-fluorothiophen-2-yl)-6-(pyrimidin-2-yl)-4,4a,5,6,7,7a-hexahydropyrrolo[3,4-d][1,3]thiazin-2-yl]benzamide (456 mg, 1.04 mmol) is added methanol (10.4 mL) and lithium hydroxide (218 mg, 5.19 mmol). The solution is heated to reflux for 2.5 hours under an atmosphere of nitrogen. The resulting solution is allowed to cool for a few minutes then concentrated under reduced pressure. The residue is extracted with dichloromethane (30 mL) and water (30 mL). The phases are partitioned and the aqueous phase further extracted with dichloromethane (1×30 mL). The combined dichloromethane extracts are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography eluting with dichloromethane/methanol, gradient from 99:1 to 90:10, to give the title compound (330 mg, 95%) as an amorphous white solid. ES/MS (m/e): 335.8 (M+H).

Workup

  1. temperatureThe solution is heated
  2. temperatureto reflux for 2.5 hours under an atmosphere of nitrogen
  3. temperatureto cool for a few minutes
  4. concentrationthen concentrated under reduced pressure
  5. extractionThe residue is extracted with dichloromethane (30 mL) and water (30 mL)
  6. customThe phases are partitioned
  7. extractionthe aqueous phase further extracted with dichloromethane (1×30 mL)
  8. dry with materialThe combined dichloromethane extracts are dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is purified by silica gel chromatography
  12. washeluting with dichloromethane/methanol, gradient from 99:1 to 90:10

Sources & evidence

ORD record
ord-aaf8658a900d48e48ce5775a379ed05e
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

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