Sodium Sulfate → HCID 68565229, compound

HRID 970391Notes

Reaction equation

HRID 970391 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4][C@H:3]1[F:15].[O-]S([O-])(=O)=O.[Na+].[Na+].[O:23]=[C:24]1[NH:29][C:28]2[CH:30]=[C:31]([CH:34]=O)[CH:32]=[CH:33][C:27]=2[S:26][CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)CCl.CCO>[F:15][C@H:3]1[CH:2]([NH:1][CH2:34][C:31]2[CH:32]=[CH:33][C:27]3[S:26][CH2:25][C:24](=[O:23])[NH:29][C:28]=3[CH:30]=2)[CH2:7][CH2:6][NH:5][CH2:4]1

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 5049666Sodium triacetoxyborohydrideHCID 109433483-Oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carbaldehydeHCID 112644351,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylate

Product 1

HCID 68565229HCID 68565229, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 702EthanolSolvent

Procedure

A solution of cis-4-amino-1-tert-butoxycarbonyl-3-fluoropiperidine (5a) (340 mg, 1.60 mmole) in ClCH2CH2Cl (8 mL) and EtOH (0.8 mL) was treated with anhydrous Na2SO4 (450 mg) and 3-oxo-3,4-dihydro-2-benzo[1,4]thiazine-6-carboxaldehyde (1n) (330 mg, 1.80 mmole). The resulting solution was stirred at room temperature for 6 hr, then sodium triacetoxy borohydride (500 mg, 2.40 mmole) was added. The resulting slurry was stirred at room temperature for a further 10 hr, then was quenched by the addition of water (2 mL) and the volatiles were removed in vacuo. The residue was partitioned between EtOAc (2×50 mL) and brine (20 mL). The organic phases were combined, dried (MgSO4), and concentrated in vacuo. The residue was passed through a column of silica gel (100% ethyl acetate), the eluant was concentrated in vacuo and the residue was disolved in 10 mL of CH2Cl2 and treated with 1.25 mL of 4N HCl in dioxane for 2 h. The volitiles were removed in vacuo and the residue was dissolved in 10 mL of CH3OH. MP-carbonate resin (1.08 g) was added and stirred at rt for 1 h. The reaction was filtered to remove the resin and concentration under reduced pressure gave the desired compound as a white solid:

Workup

  1. stirringThe resulting slurry was stirred at room temperature for a further 10 hr
  2. customwas quenched by the addition of water (2 mL)
  3. customthe volatiles were removed in vacuo
  4. customThe residue was partitioned between EtOAc (2×50 mL) and brine (20 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. concentrationthe eluant was concentrated in vacuo
  8. additiontreated with 1.25 mL of 4N HCl in dioxane for 2 h
  9. customThe volitiles were removed in vacuo
  10. dissolutionthe residue was dissolved in 10 mL of CH3OH
  11. additionMP-carbonate resin (1.08 g) was added
  12. stirringstirred at rt for 1 h
  13. filtrationThe reaction was filtered
  14. customto remove
  15. concentrationthe resin and concentration under reduced pressure

Sources & evidence

ORD record
ord-aa1c28c3433e416481f15a32af0b301b
Source dataset
uspto-grants-2007_12
Patent number
US07312212B2

Reaction notes

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