Sodium cyanoborohydride [MI] → HCID 67772039, compound

HRID 1808842Notes

Reaction equation

HRID 1808842 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[F:18])[C:5]([N:7]([CH3:14])[C@@H:8]([CH:11]([CH3:13])[CH3:12])[CH:9]=O)=[O:6].Cl.[CH3:20][O:21][CH2:22][CH:23]1[CH2:26][NH:25][CH2:24]1.[B-]C#N.[Na+]>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[F:18])[C:5]([N:7]([C@@H:8]([CH:11]([CH3:13])[CH3:12])[CH2:9][N:25]1[CH2:26][CH:23]([CH2:22][O:21][CH3:20])[CH2:24]1)[CH3:14])=[O:6]

Participants

5

Reactant 3

HCID 20587905Sodium cyanoborohydride [MI]HCID 448287953-(Methoxymethyl)azetidine--hydrogen chloride (1/1)HCID 86666004HCID 86666004, compound

Product 1

HCID 67772039HCID 67772039, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

(S)-3,4-Difluoro-N-methyl-N-(3-methyl-1-oxobutan-2-yl)benzamide (Compound A2.3) (0.25 g, 0.98 mmol) in MeOH (1.5 mL) was added to 3-(methoxymethyl)azetidine hydrochloride (0.202 g, 1.47 mmol) and TEA (0.679 mL, 4.90 mmol) in MeOH (1.5 mL). Sodium cyanotrihydroborate (0.103 mL, 1.96 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 AD 5 μm 20×250 mm column and Heptan/EtOH/TEA 80/20/0.1, as mobile phase to give the title compound (69 mg, 21%). Enantiomeric excess: 99.9%. Mixture of rotamers: (400 MHz, CD3OD) δ 0.77-0.86, 0.93, 1.06, 1.70-1.90, 2.57-2.88, 2.94-3.09, 3.22-3.36, 3.40-3.57, 4.18-4.36, 7.23-7.52, 7.63-7.74. Total no of protons: 26. HRMS (M+H)+: calculated 341.2040. found 341.2051.

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-7a3b771a3f7a46dcba455c6105872aea
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

Loading…