Acetonitrile → HCID 178501098, compound

HRID 2191213Notes

Reaction equation

HRID 2191213 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([C:21]1[N:22]=[N:23][N:24]([CH3:26])[N:25]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][NH:11][C:10]2[C:15]([CH3:20])=[CH:16][C:17]([CH3:19])=[CH:18][C:9]1=2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(#N)C.[CH:53]([C@H:55]1[CH2:60][CH2:59][C@H:58]([C:61]([O:63][CH3:64])=[O:62])[CH2:57][CH2:56]1)=O>C1COCC1>[F:35][C:2]([F:34])([F:1])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[CH2:6][N:7]([C:21]1[N:22]=[N:23][N:24]([CH3:26])[N:25]=1)[C@H:8]1[CH2:14][CH2:13][CH2:12][N:11]([CH2:53][C@H:55]2[CH2:56][CH2:57][C@H:58]([C:61]([O:63][CH3:64])=[O:62])[CH2:59][CH2:60]2)[C:10]2[C:15]([CH3:20])=[CH:16][C:17]([CH3:19])=[CH:18][C:9]1=2

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 5049666Sodium triacetoxyborohydrideHCID 49847999HCID 49847999, compoundHCID 178501146HCID 178501146, compound

Product 1

HCID 178501098HCID 178501098, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Charge a flask equipped with an overhead stirrer, temperature probe, nitrogen inlet with (S)—N-(3,5-bis(trifluoromethyl)benzyl)-7,9-dimethyl-N-(2-methyl-2H-tetrazol-5-yl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-amine (5 g, 10.03 mmoles) and sodium triacetoxyborohydride (3.19 g, 15.05 mmoles) and acetonitrile (40 mL) Immerse the flask in an ice bath to cool the slurry to below about 5° C., then add (trans)-methyl 4-formylcyclohexanecarboxylate (2.99 g, 17.57 mmoles, prepared essentially according to the procedures in Houpis, I. N. et al, Tetrahedron Let. 1993, 34(16), 2593-2596 and JP490-48639) dissolved in THF (10 mL) via a syringe while maintaining the reaction mixture at or below about 5° C. Allow the reaction to warm to RT and stir overnight. Add NH4Cl (25 mL, 50% saturated aqueous solution) and separate the aqueous layer from the organic layer. The pH of the organic layer should be about 5.5. Warm the organic layer to about 45° C. and add water (16 mL). Add a seed crystal of the titled compound and cool to about 35° C. Collect the resulting solid by filtration and rinse with ACN. Dry to provide 5.80 g of the title compound.

Workup

  1. additionCharge a flask
  2. customequipped with an overhead stirrer
  3. temperatureto cool the slurry to below about 5° C.
  4. temperaturewhile maintaining the reaction mixture at or below about 5° C
  5. customthe reaction
  6. customAdd NH4Cl (25 mL, 50% saturated aqueous solution) and separate the aqueous layer from the organic layer
  7. temperatureWarm the organic layer to about 45° C.
  8. additionadd water (16 mL)
  9. additionAdd a seed crystal of the titled compound
  10. temperaturecool to about 35° C
  11. customCollect the resulting solid
  12. filtrationby filtration
  13. washrinse with ACN
  14. customDry

Sources & evidence

ORD record
ord-c0a0370f44ea40a8bb3afbe272eed5ac
Source dataset
uspto-grants-2012_12
Patent number
US08329688B2

Reaction notes

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