Sodium hydride → HCID 86686961, compound

HRID 1402098Notes

Reaction equation

HRID 1402098 reaction equation
[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([OH:12])[CH2:4][CH2:3]1.[H-].[Na+].[C:15]([C:17]1[CH:22]=[CH:21][C:20](F)=[CH:19][N:18]=1)#[N:16]>CN(C=O)C>[NH2:1][C@@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C@H:5]([O:12][C:20]2[CH:21]=[CH:22][C:17]([C:15]#[N:16])=[N:18][CH:19]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 113324532-Cyano-5-fluoropyridineHCID 86686674(1R,4S)-4-Amino-1,2,3,4-tetrahydronaphthalen-1-ol

Product 1

HCID 86686961HCID 86686961, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Intermediate A (300 mg, 1.84 mmol) was added to an ice cold stirred suspension of sodium hydride (60% in mineral oil, 221 mg, 5.52 mmol) in DMF (15 mL) and stirred for 15 min. 2-Cyano-5-fluoropyridine (224 mg, 1.84 mmol) was added and the reaction warmed to RT. After 90 min, the reaction was quenched by dropwise addition of water and the mixture partitioned between EtOAc (75 mL) and water (150 mL). The aqueous layer was then extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-5% [2M NH3 in MeOH] in DCM, to give the title compound (255 mg, 0.96 mmol, 52%). LCMS (Method 4): Rt 0.28, 1.73, m/z 266.1 [MH+].

Workup

  1. stirringstirred for 15 min
  2. customthe reaction was quenched by dropwise addition of water
  3. customthe mixture partitioned between EtOAc (75 mL) and water (150 mL)
  4. extractionThe aqueous layer was then extracted with EtOAc (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-fe1a14f52a1447aeacc7f3fe219c7daf
Source dataset
uspto-grants-2014_12
Patent number
US08907094B2

Reaction notes

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