Acetic Acid → 2-Fluoro-4-methyl-6-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenol

HRID 1798931Notes

Reaction equation

HRID 1798931 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([NH2:9])[C:3]=1[OH:10].[CH3:11][C:12]1([N:18]2[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C([BH3-])#N.C(O)(=O)C>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([NH:9][CH:21]2[CH2:22][CH2:23][N:18]([C:12]3([CH3:11])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[CH2:19][CH2:20]2)[C:3]=1[OH:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 552821212-Amino-6-fluoro-4-methylphenolHCID 596832511-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinone

Product 1

HCID 582873142-Fluoro-4-methyl-6-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenolYield 46.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Amino-6-fluoro-4-methylphenol (D16, 49 mg, 0.34 mmol) was dissolved in DCM (3 mL) and 1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinone (D12, 68 mg, 0.34 mmol), polymer supported cyanoborohydride (160 mg, 0.69 mmol, 4.3 mmol/g) and acetic acid (0.10 mL, 1.72 mmol) were all added at room temperature. The mixture was reacted at 100° C. in the microwave for 10 min. The mixture was then cooled to room temperature, filtered and the solvent was removed under vacuum to give the crude product, an orange oil, which was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM) to give 2-fluoro-4-methyl-6-{[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]amino}phenol (D17, 51 mg, 42%) as a white solid.

Workup

  1. additionall added at room temperature
  2. customThe mixture was reacted at 100° C. in the microwave for 10 min
  3. filtrationfiltered
  4. customthe solvent was removed under vacuum
  5. customto give the crude product
  6. customan orange oil, which was purified via flash column chromatography (silica, DCM to 0.5% NH3/9.5% MeOH/90% DCM)

Sources & evidence

ORD record
ord-7c439d1ca1684e288645f75c87fb64af
Source dataset
uspto-grants-2013_01
Patent number
US08344000B2

Reaction notes

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