Piconol → HCID 86690115, compound

HRID 520404Notes

Reaction equation

HRID 520404 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][OH:8].[F:9][C:10]1([F:20])[CH2:15][O:14][C:13]([CH3:19])([C:16](O)=[O:17])[CH2:12][CH2:11]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[F:20][C:10]1([F:9])[CH2:15][O:14][C:13]([CH3:19])([C:16]([O:8][CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[O:17])[CH2:12][CH2:11]1

Participants

7

Reactant 4

HCID 11474PiconolHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86690113HCID 86690113, compound

Product 1

HCID 86690115HCID 86690115, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of pyridin-2-ylmethanol (91 mg, 0.833 mmol), 5,5-difluoro-2-methyltetrahydro-2H-pyran-2-carboxylic acid (100 mg, 0.555 mmol), HBTU (274 mg, 0.722 mmol) and DIEA (0.2 ml, 1.145 mmol) in DCM (2 mL) was stirred at rt for 4 h. The reaction mixture was diluted with EtOAc and washed with NaHCO3, brine, dried (MgSO4), concentrated and the residue was purified by silica gel chromatography (EtOAc/hexane) to afford pyridin-2-ylmethyl 5,5-difluoro-2-methyltetrahydro-2H-pyran-2-carboxylate as racemate. Two enantiomers (elute-1 @ 4.04 min and elute-2 @ 4.61 min) were separated by chiral SFC (Chiralpak AD-H preparative column, 20×250 mm, 5 μm, mobile Phase: 10% 2:1 heptane:EtOH in CO2, 150 bar; temp: 35° C.; flow rate: 45 mL/min, UV: 258 nm).

Workup

  1. washwashed with NaHCO3, brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customthe residue was purified by silica gel chromatography (EtOAc/hexane)

Sources & evidence

ORD record
ord-ca409c03c57d46dfacb77d7630db2491
Source dataset
uspto-grants-2016_05
Patent number
US09326973B2

Reaction notes

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