Methanol → HCID 49847999, compound

HRID 2191212Notes

Reaction equation

HRID 2191212 reaction equation
C([O-])=O.[NH4+].[F:5][C:6]([F:49])([F:48])[C:7]1[CH:8]=[C:9]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[CH2:10][N:11]([C:35]1[N:36]=[N:37][N:38]([CH3:40])[N:39]=1)[C@H:12]1[CH2:18][CH2:17][CH2:16][N:15](C(OCC2C=CC=CC=2)=O)[C:14]2[C:29]([CH3:34])=[CH:30][C:31]([CH3:33])=[CH:32][C:13]1=2.CO>[Pd]>[F:48][C:6]([F:5])([F:49])[C:7]1[CH:8]=[C:9]([CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=1)[CH2:10][N:11]([C:35]1[N:36]=[N:37][N:38]([CH3:40])[N:39]=1)[C@H:12]1[CH2:18][CH2:17][CH2:16][NH:15][C:14]2[C:29]([CH3:34])=[CH:30][C:31]([CH3:33])=[CH:32][C:13]1=2

Participants

5

Reactant 3

HCID 887MethanolHCID 2723923Ammonium formateHCID 86649378HCID 86649378, compound

Product 1

HCID 49847999HCID 49847999, compoundYield 45.5%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Charge a 1 L flask with ammonium formate salt (39.0 g, 618.0 mmoles) and 10% Pd/C (3.91 g) and (S)-benzyl 5-((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)-7,9-dimethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate (39.1 g, 61.8 mmoles) dissolved in MeOH (391 mL, 966 moles). Stir the resulting slurry at RT and monitor by HPLC. After the reaction is complete, filter to collect the solid. Rinse the solid with MeOH (100 mL). Combine the filtrate solutions and organic washes and then dry over Na2SO4. Filter and concentrate to dryness. Dissolve in MeOH (92 mL) and seed with seed crystals of the titled compound. Cool and store over night to yield 14.03 g, 45.5% of the titled compound, 99.92% ee by HPLC.

Workup

  1. filtrationfilter
  2. customto collect the solid
  3. washRinse the solid with MeOH (100 mL)
  4. dry with materialCombine the filtrate solutions and organic washes and then dry over Na2SO4
  5. filtrationFilter
  6. concentrationconcentrate to dryness
  7. dissolutionDissolve in MeOH (92 mL)
  8. temperatureCool

Sources & evidence

ORD record
ord-ce10d97356bf419cb00c10759c278321
Source dataset
uspto-grants-2012_12
Patent number
US08329688B2

Reaction notes

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