Formaldehyde → HCID 24994258, compound

HRID 1991356Notes

Reaction equation

HRID 1991356 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:24][CH2:23][C@@H:22]3[C@@H:18]([CH2:19][NH:20][CH2:21]3)[C@@H:17]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C=O.[C:36]([O-])(=O)C.[Na+].[BH4-].[Na+]>CO.O>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([C@H:13]([O:15][C@H:16]2[CH2:24][CH2:23][C@@H:22]3[C@@H:18]([CH2:19][N:20]([CH3:36])[CH2:21]3)[C@@H:17]2[C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 517045Sodium AcetateHCID 4311764Sodium borohydrideHCID 21099325HCID 21099325, compound

Product 1

HCID 24994258HCID 24994258, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 30 mg (0.063 mmol) of (3aR,4R,5S,7aR)-5-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-4-(4-fluorophenyl)octahydro-1H-isoindole (Example 2) in ˜2 mL methanol was added ˜20 mg (excess) aq. formaldehyde and 40 mg sodium acetate. The resulting mixture was stirred at RT for 10 min then 20 mg of NaBH4 was added. The resulting mixture was stirred at RT for 1 hr then water was added. The methanol was evaporated under vacuum and residue extracted with ether (2×25 mL). The combined extracts were dried over drying agent, filtered and the solvent was evaporated under vacuum. The residue was purified by prep TLC eluting with EtOAc/MeOH (9/1) to give the title compound. 1H-NMR (CDCl3): δ: ppm. 7.68 (1H, s), 7.23 (2H, s), 7.02 (2H, m), 6.87 (2H, m), 4.45 (1H, m), 3.27 (1H, ), 2.78-2.65 (2H, m), 2.57 (2H, m), 2.45-2.30 (3H, m), 2.23-2.12 (2H, m), 1.98 (1H, m), 1.83-1.68 (2H, m), 1.30 (3H, 6.2) MS: (MH)+489.9.

Workup

  1. stirringThe resulting mixture was stirred at RT for 1 hr
  2. customThe methanol was evaporated under vacuum and residue
  3. extractionextracted with ether (2×25 mL)
  4. customThe combined extracts were dried
  5. customover drying agent
  6. filtrationfiltered
  7. customthe solvent was evaporated under vacuum
  8. customThe residue was purified by prep TLC
  9. washeluting with EtOAc/MeOH (9/1)

Sources & evidence

ORD record
ord-7d634e725ece466583b08efe3fec100d
Source dataset
uspto-grants-2010_01
Patent number
US07645790B2

Reaction notes

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