Acetic Acid → HCID 67772409, compound

HRID 1808839Notes

Reaction equation

HRID 1808839 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.C(O)(=O)C.[F:12][C:13]1[CH:28]=[CH:27][C:16]([C:17]([N:19]([CH3:26])[C@@H:20]([CH:23]([CH3:25])[CH3:24])[CH:21]=O)=[O:18])=[CH:15][C:14]=1[CH3:29].[Na].[OH-].[Na+]>C(Cl)Cl>[F:12][C:13]1[CH:28]=[CH:27][C:16]([C:17]([N:19]([C@@H:20]([CH:23]([CH3:24])[CH3:25])[CH2:21][N:1]2[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]2)[CH3:26])=[O:18])=[CH:15][C:14]=1[CH3:29]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 79341Piperidin-4-olHCID 5360545SodiumHCID 86666002HCID 86666002, compound

Product 1

HCID 67772409HCID 67772409, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Piperidin-4-ol (0.048 g, 0.48 mmol) and acetic acid (0.032 mL, 0.56 mmol) was added to (S)-4-fluoro-N,3-dimethyl-N-(3-methyl-1-oxobutan-2-yl)benzamide (Compound A2.1) (0.1 g, 0.40 mmol) in DCM (3 mL). The resultant mixture was stirred at rt for 30 min before sodium triacetoxyhydroborate (0.101 g, 0.48 mmol) was added. The stirring was continued at rt for 3 h. NaOH (1 N aq.) was added to the mixture. The organic phase was 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 AD 5 μm 20×250 mm column and Heptan/EtOH/TEA 80/20/0.1, as mobile phase to give the title compound (29 mg, 22%). Enantiomeric excess: 99.9%. Mixture of rotamers: (600 MHz, CD3OD) δ 0.82-1.08, 1.43-1.63, 1.71-2.06, 2.12-2.51, 2.54-2.81, 2.89, 2.97-3.09, 3.27-3.46, 3.51-3.65, 4.40-4.59, 7.06-7.14, 7.22-7.37. Total no of protons: 28. HRMS (M+H)+: calculated 337.2291. found 337.2268.

Workup

  1. additionwas added
  2. filtrationThe organic phase was filtered through a phase separator
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by preparative HPLC
  5. additionThe product containing fractions
  6. concentrationwas concentrated
  7. customthe residue was purified a second time by preparative HPLC

Sources & evidence

ORD record
ord-d8390ec25bb34776b18b76c2bfc39531
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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