Triethylamine → 4-[4-(4-Fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl ester

HRID 2288106Notes

Reaction equation

HRID 2288106 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH2:12])[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].C(N(CC)CC)C.[F:20][C:21]1[CH:37]=[CH:36][C:24]([O:25][C:26]2[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=2)=[CH:23][CH:22]=1.C(OCC)(=O)C.CCCCCC>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1([NH:12][S:32]([C:29]2[CH:30]=[CH:31][C:26]([O:25][C:24]3[CH:36]=[CH:37][C:21]([F:20])=[CH:22][CH:23]=3)=[CH:27][CH:28]=2)(=[O:33])=[O:34])[CH2:7][CH2:8][O:9][CH2:10][CH2:11]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27827574-(4-Fluorophenoxy)benzenesulphonyl chlorideHCID 21226206Ethyl acetate hexane2×HCID 544950714-Aminotetrahydro-2H-pyran-4-carboxylic acid ethyl ester

Product 1

HCID 544554294-[4-(4-Fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-aminotetrahydropyran-4-carboxylic acid ethyl ester (7.00 grams, 0.0404 mole) in N,N-dimethylformamide (40 mL) was added triethylamine (5.94 mL, 0.043 mole). Solid 4-(4-fluorophenoxy)benzenesulfonyl chloride (12.165 grams, 0.0424 mole) was added in portions. The resulting mixture was stirred at room temperature for 16 hours and then most of the solvent was removed by evaporation under vacuum. The residue was partitioned between saturated sodium bicarbonate solution and dichloromethane. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine and dried over sodium sulfate. Evaporation of the solvent under vacuum provided crude 4-[4-(4-fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl ester as an amber oil (21.05 grams). Flash chromatography on silica gel eluting with 25% ethyl acetate/hexane followed by 50% ethyl acetate/hexane provided 4-[4-(4-fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl ester as an off-white crystalline solid (12.15 grams, 71%, mp 116-117° C.).

Workup

  1. custommost of the solvent was removed by evaporation under vacuum
  2. customThe residue was partitioned between saturated sodium bicarbonate solution and dichloromethane
  3. extractionThe aqueous layer was extracted with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customEvaporation of the solvent under vacuum
  7. customprovided crude 4-[4-(4-fluorophenoxy)benzenesulfonylamino]tetrahydropyran-4-carboxylic acid ethyl ester as an amber oil (21.05 grams)

Sources & evidence

ORD record
ord-a3744ea56dee4036a1f3c17e86645e4e
Source dataset
uspto-grants-2000_07
Patent number
US06087392

Reaction notes

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