Sodium borohydride → HCID 69448198, compound

HRID 860171Notes

Reaction equation

HRID 860171 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:25])[CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[N:18]([CH2:23][CH3:24])[N:19]=[C:20]([CH3:22])[CH:21]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1.[BH4-].[Na+]>CCO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:25])[CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[N:18]([CH2:23][CH3:24])[N:19]=[C:20]([CH3:22])[CH:21]=3)[CH2:13][CH2:12]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 69444554HCID 69444554, compound

Product 1

HCID 69448198HCID 69448198, compoundYield 33.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of the product of Step 1 (90 mg, 0.25 mmol), in EtOH (10 mL) was treated with NaBH4 (38 mg, 1.0 mmol) and stirred at RT for 1 h. The reaction was quenched with NH4Cl solution, then the EtOH was removed under reduced pressure. The residue was partitioned between CH2Cl2 and water and the organic layer separated and the aqueous re-extracted with CH2Cl2. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to give 1-(4-chloro-phenyl)-3-[4-(2-ethyl-5-methyl-2H-pyrazol-3-yl)-piperidin-1-yl]-propan-1-ol as a gum (30 mg). This intermediate was dissolved in THF (5 mL), treated with N-methylbenzenesulfonamide (17 mg, 0.1 mmol), PPh3 (26 mg, 0.1 mmol) and DIAD (20 μL, 0.1 mmol) and stirred overnight at RT. The solvent was evaporated under reduced pressure and the residue dissolved in CH2Cl2 and loaded onto a 5 g SCX cartridge, which was eluted with CH2Cl2 then 2M NH3 in MeOH solution. The fractions containing the desired material were concentrated under reduced pressure and were further purified by silica chromatography eluting 1–3% MeOH/CH2Cl2 to yield the desired sulfonamide. 1H NMR (CDCl3, 400 MHz) δ 7.70 (2H, d, J=7.3 Hz), 7.48 (1H, d, J=7.3 Hz), 7.40 (2H, t, J=7.3 Hz), 7.20–7.15 (2H, m), 7.07 (2H, d, J=8.4 Hz), 5.73 (1H, s), 5.07 (1H, t, J=7.3 Hz), 3.94 (2H, q, J=7.4 Hz), 2.92–2.68 (2H, m), 2.60 (3H, s), 2.48–2.32 (1H, m), 2.28–2.05 (5H, m), 2.05–1.40 (8H, m), 1.33 (3H, t, J=7.4 Hz). MS (ES+) C27H35ClN4O2S requires: 515, found: 515/517 (3:1, M+H+)

Workup

  1. customThe reaction was quenched with NH4Cl solution
  2. customthe EtOH was removed under reduced pressure
  3. customThe residue was partitioned between CH2Cl2 and water
  4. customthe organic layer separated
  5. extractionthe aqueous re-extracted with CH2Cl2
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-15e5ef25b94a473da12441d1ed40ae4f
Source dataset
uspto-grants-2006_12
Patent number
US07153868B2

Reaction notes

Loading…