2-Aminophenol → 4-[[4-[3-(2-benzoxazolyl)propoxy]phenyl]sulfonyl]tetrahydro-N-hydroxy-2H-pyran-4-carboxamide

HRID 2181388Notes

Reaction equation

HRID 2181388 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([C:17]2([C:23]([O:25]C(C)(C)C)=O)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)(=[O:16])=[O:15])=[CH:10][CH:9]=1)(O)=[O:2].Cl.CN(C)CCCN=C=NCC.[OH:42][N:43]1C2C=CC=CC=2N=N1.[NH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1O.CN1CCOCC1>CN(C)C=O>[O:2]1[C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=2[N:52]=[C:1]1[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([S:14]([C:17]2([C:23]([NH:43][OH:42])=[O:25])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)(=[O:15])=[O:16])=[CH:12][CH:13]=1

Participants

7

Reactant 5

HCID 58012-AminophenolHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 865907724-[[4-(3-carboxypropoxy)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,1-dimethylethyl ester

Product 1

HCID 224844124-[[4-[3-(2-benzoxazolyl)propoxy]phenyl]sulfonyl]tetrahydro-N-hydroxy-2H-pyran-4-carboxamideYield 92.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Part A. To a solution of 4-[[4-(3-carboxypropoxy)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,1-dimethylethyl ester (3.0 g, 7.0 mmol) in N,N-dimethylformamide (14 mL) was added 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (1.88 g, 9.8 mmol) and 1-hydroxybenzotriazole (1.32 g, 9.8 mmol). The resulting suspension became a clear amber solution after stirring at 50° C. for 1.5 hr. The reaction was then treated with 2-aminophenol (0.76 g, 7.0 mmol), followed by N-methylmorpholine (2.3 mL, 21.0 mmol). The reaction was stirred at 50° C. overnight. After 21 hr, the reaction was partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate. The organic layers were combined and washed with saturated sodium bicarbonate solution, water, 1:1 solution of water:brine, and brine; dried over sodium sulfate; filtered; and concentrated in vacuo. The resulting oil was purified on silica gel using ethyl acetate/hexanes to afford 2.98 g (82%) of the amide as an amber oil. ESMS m/z=542 [M+Na]+.

Workup

  1. stirringThe reaction was stirred at 50° C. overnight
  2. waitAfter 21 hr
  3. customthe reaction was partitioned between ethyl acetate (50 mL) and water (50 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washwashed with saturated sodium bicarbonate solution, water, 1:1 solution of water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationand concentrated in vacuo
  9. customThe resulting oil was purified on silica gel

Sources & evidence

ORD record
ord-0f5ea331acd04facb6022f5bf1e9cd22
Source dataset
uspto-grants-2005_05
Patent number
US06890928B2

Reaction notes

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