Stannous Chloride → HCID 66684116, compound

HRID 579202Notes

Reaction equation

HRID 579202 reaction equation
C[O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[CH:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][CH2:13][C@H:12]([N:22]=[N+]=[N-])[C:11]1=[O:25])=[O:4].Cl[Sn]Cl.O[Li].O>CO>[NH2:22][C@H:12]1[CH2:13][CH2:14][CH:15]([CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)[N:10]([C:9]2[CH:8]=[C:7]([C:26]#[C:27][C:28]([CH3:30])([CH3:31])[CH3:29])[S:6][C:5]=2[C:3]([OH:4])=[O:2])[C:11]1=[O:25]

Participants

5

Reactant 3

HCID 24479Stannous ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 86684773HCID 86684773, compound

Product 1

HCID 66684116HCID 66684116, compoundYield 33.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the solution of 3-((S)-3-azido-6-cyclohexyl-2-oxo-piperidin-1-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (40 mg, 0.09 mmol, 1 equiv) in MeOH (0.5 mL) was added SnCl2 (17 mg, 0.09 mmol, 1 equiv) and the resulting solution was stirred at room temperature for 18 hours. The solvent was then removed under vacuum. The residue was dissolved in THF/H2O/MeOH (0.5 mL/0.5 mL/1.0 mL) and to the solution was added LiOH.H2O (21 mg, 0.48 mmol, 5 equiv). The reaction mixture was stirred at 50° C. for 20 minutes. The organic solvents were removed under vacuum and the residue was acidified to pH=5 by addition of 3.0 N HCl aq. solution. The mixture was extracted with EtOAc. The organic layer was dried over Na2SO4, and concentrated under vacuum. The residue was purified by prep-HPLC (XBridge Prep C 18 5 um, 30×50 mm) in basic condition (0.1% NH4OH, 10%˜45% CH3CN/H2O, 10 min run, 40 ml/min) to give product 12 mg. MS: 403 [M+H+]. 1H-NMR (400 MHZ, CD3OD): δ 6.81 (s, 1H), 3.96 (br, 1H), 3.48 (m, 1H), 2.06 (m, 3H), 1.84 (m, 3H), 1.70 (br, 2H), 1.46 (m, 1H), 1.37 (m, 1H), 1.31 (s, 9H), 1.16 (m, 5H).

Workup

  1. customThe solvent was then removed under vacuum
  2. dissolutionThe residue was dissolved in THF/H2O/MeOH (0.5 mL/0.5 mL/1.0 mL) and to the solution
  3. stirringThe reaction mixture was stirred at 50° C. for 20 minutes
  4. customThe organic solvents were removed under vacuum
  5. additionthe residue was acidified to pH=5 by addition of 3.0 N HCl aq. solution
  6. extractionThe mixture was extracted with EtOAc
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by prep-HPLC (XBridge Prep C 18 5 um, 30×50 mm) in basic condition (0.1% NH4OH, 10%˜45% CH3CN/H2O, 10 min run, 40 ml/min)

Sources & evidence

ORD record
ord-2437422a05fa4a67b6604f8553c583e9
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

Loading…