Hydrochloric Acid → 4-(2-Hydroxy-3-methyl-benzoylamino)-tetrahydro-thiopyran-4-carboxylic acid methyl ester

HRID 1047684

Reaction equation

HRID 1047684 reaction equation
Cl.[CH3:2][O:3][C:4]([C:6]1([NH2:12])[CH2:11][CH2:10][S:9][CH2:8][CH2:7]1)=[O:5].[OH:13][C:14]1[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:15]=1[C:16](O)=[O:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:2][O:3][C:4]([C:6]1([NH:12][C:16](=[O:17])[C:15]2[CH:19]=[CH:20][CH:21]=[C:22]([CH3:23])[C:14]=2[OH:13])[CH2:7][CH2:8][S:9][CH2:10][CH2:11]1)=[O:5]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 67383-Methylsalicylic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 15524434Methyl 4-aminothiane-4-carboxylate

Product 1

HCID 593142624-(2-Hydroxy-3-methyl-benzoylamino)-tetrahydro-thiopyran-4-carboxylic acid methyl esterYield 13.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of HCl salt of 4-amino-tetrahydro-thiopyran-4-carboxylic acid methyl ester (529 mg, 2.5 mmol), 2-hydroxy-3-methyl-benzoic acid (380 mg, 2.5 mmol), HATU (1.14 g, 3.0 mmol) in anhydrous DMF (20 mL) is added DIPEA (1.66 mL, 10 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (30 mL) and washed with water (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane) to give a pure product (27) as white solid (102 mg, 13%).

Workup

  1. customAfter the removal of DMF in vacuo
  2. dissolutionthe residue is dissolved in EtOAc (30 mL)
  3. washwashed with water (1×10 mL) and brine (2×10 mL)
  4. dry with materialThe organic layer is dried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by flash column chromatography (115 g silica gel, gradient elution: 10-80% EtOAc in heptane)

Sources & evidence

ORD record
ord-fb5b094bc0f940f4bcca61c454ca535d
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Linked notes

Loading…