4-Toluenesulfonyl chloride → Toluene-4-sulfonic acid 3-[4-(1-tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)-phenyl]-1-methylpropyl ester

HRID 1479257Notes

Reaction equation

HRID 1479257 reaction equation
C([N:5]1[C:10](=[O:11])[C:9]([Cl:12])=[C:8]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH:23]([OH:25])[CH3:24])=[CH:17][CH:16]=2)[CH:7]=[N:6]1)(C)(C)C.[C:26]1([CH3:36])[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>N1C=CC=CC=1.C(OCC)(=O)C>[C:15]([CH:14]([O:13][C:8]1[CH:7]=[N:6][NH:5][C:10](=[O:11])[C:9]=1[Cl:12])[C:15]1[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][CH:23]([O:25][S:32]([C:29]2[CH:30]=[CH:31][C:26]([CH3:36])=[CH:27][CH:28]=2)(=[O:34])=[O:33])[CH3:24])=[CH:19][CH:20]=1)([CH3:20])([CH3:16])[CH3:14]

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 596786062-tert-butyl-4-chloro-5-[4-(3-hydroxybutyl)benzyloxy]-2H-pyridazin-3-one

Product 1

HCID 86600388Toluene-4-sulfonic acid 3-[4-(1-tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4-yloxymethyl)-phenyl]-1-methylpropyl esterYield 52%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Example 7B (200 mg, 0.548 mmol) in pyridine (10 mL) was added p-toluenesulfonyl chloride (209 mg, 1.096 mmol). The reaction was stirred at room temperature overnight under nitrogen atmosphere. Monitoring by LC-MS showed a 1:1 mixture of starting material and product. The reaction was diluted with ethyl acetate and washed with 5% CuSO4 until a light blue aqueous solution was maintained. The organic layer was then dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash column chromatography (3:1 hexane:ethyl acetate to 100% ethyl acetate) to recover the starting material (90 mg) and the product as a clear oil (74 mg, 47% yield based on recovered starting material). 1H NMR (600 MHz, CDCl3): 7.80 (d, 2H, J=8.3 Hz), 7.72 (s, 1H), 7.33 (d, 2H, J=8.0 Hz), 7.30 (d, 2H, J=8.1 Hz), 7.13 (d, 2H, J=8.1 Hz), 5.27 (s, 2H), 4.66 (m, 1H), 2.65 (m, 1H), 2.54 (m, 1H), 2.45 (s, 3H), 1.94 (m, 1H), 1.81 (m, 1H), 1.63 (s, 9H), 1.26 (s, 3H).

Workup

  1. additiona 1:1 mixture of starting material and product
  2. washwashed with 5% CuSO4 until a light blue aqueous solution
  3. temperaturewas maintained
  4. dry with materialThe organic layer was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash column chromatography (3:1 hexane:ethyl acetate to 100% ethyl acetate)
  8. customto recover the starting material (90 mg)

Sources & evidence

ORD record
ord-9204d1de756345a09b77f18614ac6501
Source dataset
uspto-grants-2016_08
Patent number
US09408927B2

Reaction notes

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