2,2,2-Cryptand → (+/-)-2-tert-butyl-4-chloro 5-(4-(1-fluoro-but-2-oxy)benzyl)oxy-3(2H)-pyridazinone

HRID 1751825Notes

Reaction equation

HRID 1751825 reaction equation
[C:1]([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]([O:21][CH:22]([CH2:35][CH3:36])[CH2:23]OS(C3C=CC(C)=CC=3)(=O)=O)=[CH:17][CH:16]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[F-:37].[K+].C1N2CCOCCOCCN(CCOCCOCC2)CCOCCOC1>C(#N)C>[C:1]([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]([O:21][CH:22]([CH2:35][CH3:36])[CH2:23][F:37])=[CH:17][CH:16]=2)[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 728012,2,2-CryptandHCID 522689Potassium FluorideHCID 59678622(+/-)-2-tert-butyl 4-chloro 5-(4-(1-tosyloxy-but-2-oxy) benzyl)oxy 3(2H)-pyridazinone

Product 1

HCID 44576650(+/-)-2-tert-butyl-4-chloro 5-(4-(1-fluoro-but-2-oxy)benzyl)oxy-3(2H)-pyridazinoneYield 65%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

The product of Example 3F (28 mg, 52.4 mop was dissolved in 0.5 mL acetonitrile in a 5 mL flask and to this was added a solution of potassium fluoride (4.5 mg, 78.6 μmol) and Kryptofix 222 (29.6 mg, 78.6 μmol) in 0.5 mL acetonitrile. The above solution was then immersed in a oil bath preheated to 90° C. The reaction was allowed to stir for 90 minutes after which all the volatiles were removed under reduced pressure and the crude mixture purified by preparative thin layer chromatography to obtain 13 mg (65%) of pure desired compound. 1H (CDCl3) δ (ppm): 7.72 (s, 1H), 7.3 (d, 2H), 6.9 (d, 2H), 5.23 (s, 2H), 4.57-4.59 (m, 2H), 4.4 (m, 4H), 1.74 (m, 2H), 1.6 (s, 9H), 1.0 (t, 3H). 13C (CDCl3) δ (ppm): 159, 158.7, 153.7, 129, 127.5, 125.2, 118.3, 116.4, 83.85 (d, 1JCF=172.2), 78, 71.1, 66.3, 27.8, 23.2, 9.48. 19F (CDCl3, CFCl3 as internal standard) δ (ppm): −228 (d of t, J=−19, −60 Hz)

Workup

  1. customThe above solution was then immersed in a oil bath
  2. custompreheated to 90° C
  3. customwere removed under reduced pressure
  4. customthe crude mixture purified by preparative thin layer chromatography

Sources & evidence

ORD record
ord-a8b90635a8a444118d56967e72e27aed
Source dataset
uspto-grants-2015_10
Patent number
US09161997B2

Reaction notes

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