Acetic Acid → HCID 58284649, compound

HRID 1623325Notes

Reaction equation

HRID 1623325 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[F:9][C:10]1([CH:16]=O)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C([O-])(O)=O.[Na+].Cl>[Br:1][C:2]1[N:7]=[C:6]([NH:8][CH2:16][C:10]2([F:9])[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 3008092-Amino-6-bromopyridineHCID 5049666Sodium triacetoxyborohydrideHCID 707011204-Fluorooxane-4-carbaldehyde

Product 1

HCID 58284649HCID 58284649, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To 6-bromopyridin-2-amine (3.03 g, 17.50 mmol) was added the crude solution of 4-fluorotetrahydro-2H-pyran-4-carbaldehyde in DCM. To the mixture was added acetic acid (1.002 mL, 17.50 mmol) and sodium triacetoxyborohydride (5.56 g, 26.3 mmol) in portions. The mixture was stirred for 2 hr at ambient temperature. The mixture was diluted carefully with saturated aqueous NaHCO3 solution. The separated aqueous layer was extracted with DCM (1×). The combined organic layers were washed with water (1×), saturated aqueous NaHCO3 solution (1×) and concentrated in vacuo. The solid resulting residue was dissolved in DCM (100 mL) and 3M aqueous HCl (60 mL). The separated organic layer was extracted with 3M aqueous HCl (3×20 mL). The combined acidic layers were washed with DCM (1×). Solid NaHCO3 was added carefully to the acidic solution [Caution: gas development!] until pH>˜8. The aqueous mixture was extracted with DCM (2×) and EtOAc (2×). The combined organic layers were concentrated in vacuo. The resulting residue was dissolved in EtOAc. The solution was washed with 0.3M aqueous HCl, and brine, dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/heptane=5/95 for 3 min, then EtOAc/heptane=5/95 to 30/70 over 15 min, then EtOAc/heptane=30/70] providing 6-bromo-N-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine as a white solid. Yield: 1.82 g. LCMS (m/z): 288.9/291.0 [M+H]+; Retention time=0.84 min.

Workup

  1. extractionThe separated aqueous layer was extracted with DCM (1×)
  2. washThe combined organic layers were washed with water (1×), saturated aqueous NaHCO3 solution (1×)
  3. concentrationconcentrated in vacuo
  4. customThe solid resulting residue
  5. extractionThe separated organic layer was extracted with 3M aqueous HCl (3×20 mL)
  6. washThe combined acidic layers were washed with DCM (1×)
  7. additionSolid NaHCO3 was added carefully to the acidic solution [Caution: gas development!] until pH>˜8
  8. extractionThe aqueous mixture was extracted with DCM (2×) and EtOAc (2×)
  9. concentrationThe combined organic layers were concentrated in vacuo
  10. dissolutionThe resulting residue was dissolved in EtOAc
  11. washThe solution was washed with 0.3M aqueous HCl, and brine
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered off
  14. concentrationconcentrated in vacuo
  15. customThe resulting residue was purified by column chromatography [SiO2, 40 g, EtOAc/heptane=5/95 for 3 min
  16. waitEtOAc/heptane=5/95 to 30/70 over 15 min

Sources & evidence

ORD record
ord-6962ffaa17f54ab9bc3a93d8e39c86e6
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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