HCID 57986843, compound → HCID 44251825, compound

HRID 1516518Notes

Reaction equation

HRID 1516518 reaction equation
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([O:10][CH2:11][C:12]3[N:13]=[C:14]([CH:17]4[CH2:22][CH2:21][N:20]([C:23]#[N:24])[CH2:19][CH2:18]4)[S:15][CH:16]=3)=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1.[OH:27][NH:28][C:29](=N)[CH:30]([CH3:32])[CH3:31]>C1COCC1.[Cl-].[Zn+2].[Cl-]>[CH:30]([C:29]1[N:24]=[C:23]([N:20]2[CH2:21][CH2:22][CH:17]([C:14]3[S:15][CH:16]=[C:12]([CH2:11][O:10][C:9]4[CH:8]=[CH:7][C:6]([N:1]5[CH:5]=[N:4][N:3]=[N:2]5)=[CH:26][CH:25]=4)[N:13]=3)[CH2:18][CH2:19]2)[O:27][N:28]=1)([CH3:32])[CH3:31]

Participants

5

Reactant 2

HCID 57986843HCID 57986843, compoundHCID 178449908HCID 178449908, compound

Product 1

HCID 44251825HCID 44251825, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-[4-(4-Tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidine-1-carbonitrile (0.450, 1.22 mmol) and N-hydroxy-isobutyramidine (0.150 g, 1.47 mmol) in dry THF (10 mL) was added a 1 M solution of zinc chloride in THF (1.47 mL, 1.47 mmol) over 15 min. The suspension was left to settle for 15 minutes and the white precipitate was collected by filtration and dissolved in 4N HCl in ethanol and water (1:1). The solution was refluxed for 1 hour, cooled and the solid precipitate was filtered off. The filtrate was neutralized by the addition of excess sodium carbonate. The excess was filtered off and the filtrate was diluted with EtOAc. The solution was washed with water, separated, dried (Na2SO4), filtered and concentrated. The residual oil was chromatographed on silica gel (1:1 Hex/EtOAc) to afford the desired compound. 1H NMR (CDCl3): δ 8.92 (1H, s), 7.62 (2H, d), 7.28 (1H, s), 7.19 (2H, d), 5.24 (2H, s), 4.26 (2H, m), 3.20 (3H, m), 2.89 (1H, m), 2.26 (2H, m), 1.92 (2H, m), 1.30 (6H, d).

Workup

  1. waitThe suspension was left
  2. filtrationthe white precipitate was collected by filtration
  3. dissolutiondissolved in 4N HCl in ethanol
  4. temperatureThe solution was refluxed for 1 hour
  5. temperaturecooled
  6. filtrationthe solid precipitate was filtered off
  7. additionThe filtrate was neutralized by the addition of excess sodium carbonate
  8. filtrationThe excess was filtered off
  9. additionthe filtrate was diluted with EtOAc
  10. washThe solution was washed with water
  11. customseparated
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residual oil was chromatographed on silica gel (1:1 Hex/EtOAc)

Sources & evidence

ORD record
ord-a65bff42696b4f4eaffc91528bf06cda
Source dataset
uspto-grants-2012_07
Patent number
US08227495B2

Reaction notes

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