Triethylamine → HCID 22274499, compound

HRID 1064792Notes

Reaction equation

HRID 1064792 reaction equation
[F:1][C:2]([F:20])([F:19])[S:3]([O:6][C:7]1[C:12]2[CH:13]=[C:14]([CH2:16][CH2:17][OH:18])[O:15][C:11]=2[CH:10]=[CH:9][CH:8]=1)(=[O:5])=[O:4].[CH3:21][S:22](Cl)(=[O:24])=[O:23].C(N(CC)CC)C>C(Cl)Cl>[F:20][C:2]([F:1])([F:19])[S:3]([O:6][C:7]1[C:12]2[CH:13]=[C:14]([CH2:16][CH2:17][O:18][S:22]([CH3:21])(=[O:24])=[O:23])[O:15][C:11]=2[CH:10]=[CH:9][CH:8]=1)(=[O:4])=[O:5]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 22274552HCID 22274552, compound

Product 1

HCID 22274499HCID 22274499, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

As shown in Scheme 15, 2-(2-Hydroxyethyl)-1-benzofuran-4-yl trifluoromethanesulfonate, prepared as described in Examples 85A-85C herein, is treated with methanesulfonyl chloride and triethylamine in CH2Cl2 at 0° C. to provide 2-{2-[(methylsulfonyl)oxy]ethyl}-1-benzofuran-4-yl trifluoromethanesulfonate. 2-{2-[(Methylsulfonyl)oxy]ethyl}-1-benzofuran-4-yl trifluoromethanesulfonate is treated with (2R)-methylpyrrolidine mono-(L)-tartaric acid salt and Cs2CO3 in MeCN at approximately 35° C. for 1 to 4 days to provide 2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-4-yl trifluoromethanesulfonate. 2-{2-[(2R)-2-Methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-4-yl trifluoromethanesulfonate is processed as described in Murata, et al., Journal of Organic Chemistry (2000) 65, 164-168 to provide (2R)-2-methyl-1-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran-2-yl]ethyl}pyrrolidine. For example, one equivalent of 2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-4-yl trifluoromethanesulfonate is treated with palladium acetate or [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (PdCl2dppf), 3 equivalents of triethylamine, and 1.5 equivalents of pinacolborane in 1,4-dioxane at 25° C. for several hours or until the reaction is complete as judged by TLC. (2R)-2-Methyl-1-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran-2-yl]ethyl}pyrrolidine is treated with a suitable starting material, for example, aryl halides, aryl triflates, or heterocyclic halides, a palladium catalyst, such as palladium (II) acetate, a trivalent phosphine such as biphen-2-yl-dicyclohexylphosphine, and aqueous sodium carbonate or potassium phosphate in an organic solvent such as ethanol or tetrahydrofuran at 25° C. to 120° C. to provide compounds of formula (51). Compounds of formula (51) can be isolated and purified by methods known to those skilled in the art. For example, compounds of formula (51) is partitioned between dichloromethane and water, the organic phase concentrated, and the residue purified by chromatography on silica gel.

Workup

  1. customprepared

Sources & evidence

ORD record
ord-71b83d4c049f449c8017577b308a7bc5
Source dataset
uspto-grants-2005_11
Patent number
US06969730B2

Reaction notes

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