Acetic Acid → HCID 24970056, compound

HRID 604661Notes

Reaction equation

HRID 604661 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][C:28]=3[C:29]3[CH:34]=[C:33]([CH:35]([CH3:37])[CH3:36])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[CH2:25][NH:24][CH2:23]4)[C@H:14]2[CH3:41])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[BH3-][C:45]#N.[Na+].CC(O)=O.C=O>CO>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][C:28]=3[C:29]3[CH:34]=[C:33]([CH:35]([CH3:36])[CH3:37])[C:32]([F:38])=[CH:31][C:30]=3[O:39][CH3:40])[CH2:25][N:24]([CH3:45])[CH2:23]4)[C@H:14]2[CH3:41])[CH:4]=[C:3]([C:2]([F:1])([F:42])[F:43])[CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 24970055HCID 24970055, compound

Product 1

HCID 24970056HCID 24970056, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(4-fluoro-5-isopropyl-2-methoxyphenyl)-2,3-dihydro-1H-isoindol-5-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (8.3 mg, 0.0136 mmol) in MeOH (0.2 mL), was added NaCNBH3 (1.0 mg, 0.0163 mmol), AcOH (3.85 uL, 0.068 mmol) and formaldehyde (38%) (1.3 uL, 0.0176 mmol). The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was washed with sat. aq. NaHCO3. The aqueous layer was extracted with EtOAc (2×). The combined organic layers were washed with brine (1×), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(4-fluoro-5-isopropyl-2-methoxyphenyl)-2-methyl-2,3-dihydro-1H-isoindol-5-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. LCMS calc. 625.2; found=624.9 (M+H)+.

Workup

  1. washThe reaction mixture was washed with sat. aq. NaHCO3
  2. extractionThe aqueous layer was extracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine (1×)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-cbabc39533a447d0bcdd9f3e2a218b7f
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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