Acetic Acid → HCID 67774026, compound

HRID 1808841Notes

Reaction equation

HRID 1808841 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]([CH3:15])[C@@H:9]([CH:12]([CH3:14])[CH3:13])[CH:10]=O)=[O:7])=[CH:4][CH:3]=1.[NH:18]1[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]1.C(O)(=O)C.[B-]C#N.[Na+]>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]([C@@H:9]([CH:12]([CH3:14])[CH3:13])[CH2:10][N:18]2[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]2)[CH3:15])=[O:7])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 79341Piperidin-4-olHCID 20587905Sodium cyanoborohydride [MI]HCID 86666003HCID 86666003, compound

Product 1

HCID 67774026HCID 67774026, compoundYield 2.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(S)-4-Chloro-N-methyl-N-(3-methyl-1-oxobutan-2-yl)benzamide (Compound A2.2) (0.12 g, 0.47 mmol) dissolved in DCM was added to piperidin-4-ol (72 mg, 0.71 mmol) and acetic acid (0.135 mL, 2.36 mmol) in MeOH (2 mL). Sodium cyanotrihydroborate (0.059 g, 0.95 mmol) was added and the resultant mixture was stirred at rt over night. The solvent was removed and the residue diluted with DCM. The organic phase was washed with LiOH (aq., 3 mL, 1M), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC. The product containing fractions was concentrated and the residue was purified a second time by preparative HPLC using Chiralpak IC 5 μm 20×250 mm column and Heptan/EtOH/TEA 60/40/0.1, as mobile phase to give the title compound (4 mg, 2.5%). Enantiomeric excess: 99.8%. Mixture of rotamers: (600 MHz, CD3OD) δ 0.87, 0.92, 0.96, 1.03, 1.42-1.62, 1.71-1.90, 1.92-2.03, 2.14-2.21, 2.26-2.38, 2.42-2.50, 2.55-2.79, 2.88-2.93, 3.01, 3.28-3.38, 3.52-3.64, 4.43-4.56, 7.37-7.41, 7.43-7.52.

Workup

  1. customThe solvent was removed
  2. additionthe residue diluted with DCM
  3. washThe organic phase was washed with LiOH (aq., 3 mL, 1M)
  4. filtrationfiltered through a phase separator
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC
  7. additionThe product containing fractions
  8. concentrationwas concentrated
  9. customthe residue was purified a second time by preparative HPLC

Sources & evidence

ORD record
ord-a5f719b7bd044b8c970d3abbd0e98a29
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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