Sodium Hydroxide → Rilmakalim

HRID 2379788Notes

Reaction equation

HRID 2379788 reaction equation
ClCCCC(Cl)=[O:6].[OH-].[Na+].Cl[CH2:11][CH2:12][CH2:13][C:14]([NH:16][C:17]1(O)[CH2:22][C:21]([CH3:24])([CH3:23])[O:20][C:19]2[CH:25]=[CH:26][C:27]([S:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)(=[O:31])=[O:30])=[CH:28][C:18]1=2)=[O:15]>C(Cl)Cl>[CH3:24][C:21]1([CH3:23])[O:20][C:19]2[CH:25]=[CH:26][C:27]([S:29]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)(=[O:31])=[O:30])=[CH:28][C:18]=2[C@@H:17]([N:16]2[CH2:11][CH2:12][CH2:13][C:14]2=[O:15])[C@@H:22]1[OH:6]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 783704-Chlorobutyryl chlorideHCID 18956403HCID 18956403, compound

Product 1

HCID 65966Rilmakalim

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-bromo-3,4-dihydro-2,2-dimethyl-6-phenylsulfonyl-2H-benzo[b]pyran-4-ol in ethanol is shaken under a pressure of 8 bar of NH3 at 50° in an autoclave for 8 hours. The mixture is cooled and then evaporated to dryness and recrystallized from ethyl acetate. 4-Amino-3,4-dihydro-2,2-dimethyl-6-phenylsulfonyl-2H-benzo[b]pyran-3-ol of melting point: 160°-163°C. is obtained and is immediately subjected to acylation with 4-chlorobutyryl chloride. For this purpose, the substance is dissolved together with the acid chloride in CH2Cl2 and stirred in a two-phase mixture with 2N sodium hydroxide solution at room temperature for 24 hours. The usual working up results in 4-(4-chlorobutyrylamino)-3,4-di-hydro-2,2-dimethyl-6-phenylsulfonyl-2H-benzo[b]pyran-4-ol of melting point 155°-157° C. Cyclization to give the title compound is carried out by dissolving the substance in tetrahydrofuran, addition of a stoichiometric amount of 80% NaH suspension in oil and stirring the mixture at room temperature for 24 hours. The final product is identical to the product obtained by process b). Melting point: 200°-201° C. If 4-amino-3,4-dihydro-2,2-dimethyl-6-phenylsulfonyl-2H-benzo[b]pyran-3-ol is subjected to racemate resolution, it is possible to obtain from its (+) enantiomer the pure (+) enantiomer from Example 5a with the data indicated there.

Sources & evidence

ORD record
ord-ce9e8e253f3e41e0a4ec41130b7e71d1
Source dataset
uspto-grants-1994_11
Patent number
US05364878

Reaction notes

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