Benzylacetylene → Propyl [7-(5-benzyl-1H-1,2,3-triazol-1-yl)-4-fluoro-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate

HRID 570644Notes

Reaction equation

HRID 570644 reaction equation
[N:1]([CH:4]1[CH2:24][N:8]2[C:9]3[C:14]([C:15]([CH2:16][C:17]([O:19][CH2:20][CH2:21][CH3:22])=[O:18])=[C:7]2[CH2:6][CH2:5]1)=[CH:13][CH:12]=[CH:11][C:10]=3[F:23])=[N+:2]=[N-:3].[CH2:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:26]#[CH:27]>C1C=CC=CC=1.CC1C([Ru+])(C)C(C)=C(C)C=1C.ClC1CCC=CCCC=1>[CH2:25]([C:26]1[N:1]([CH:4]2[CH2:24][N:8]3[C:9]4[C:14]([C:15]([CH2:16][C:17]([O:19][CH2:20][CH2:21][CH3:22])=[O:18])=[C:7]3[CH2:6][CH2:5]2)=[CH:13][CH:12]=[CH:11][C:10]=4[F:23])[N:2]=[N:3][CH:27]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 575753BenzylacetyleneHCID 86645392Propyl (7-azido-4-fluoro-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl)acetate

Product 1

HCID 86645394Propyl [7-(5-benzyl-1H-1,2,3-triazol-1-yl)-4-fluoro-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate

Reagents, catalysts & solvents 2

HCID 178425933HCID 178425933, compoundCatalystHCID 241BenzeneSolvent

Procedure

To a stirred solution of propyl (7-azido-4-fluoro-6,7,8,9-tetrahydropyrido[1,2-α]indol-10-yl)acetate (1 eq) and prop-2-yn-1-ylbenzene (1.5 eq) in benzene (0.3M) at room temperature was added chloro(1,5-cyclooctadiene) (pentamethylcyclopentadienyl)-ruthenium(II) (0.1 eq). The reaction mixture was flushed with nitrogen then aged at 80° C. for overnight, cooled to room temperature, filtered through silica gel, washed with EtOAc and concentrated. The residue was purified by column chromatography on silica gel eluting with EtOAc/Hexane (0 to 50%) to give the desired material as a brown oil. The racemic mixture was resolved by HPLC using a 50×400 mm Chiralpak AD column eluting with 15% MeOH, 15% EtOH, 69.75% Hexanes and 0.25% Et3N at 50 mL/min and 254 nm to afford the desired chiral ester with retention time of 9.6 and 11.6 min respectively.

Workup

  1. customThe reaction mixture was flushed with nitrogen
  2. filtrationfiltered through silica gel
  3. washwashed with EtOAc
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel eluting with EtOAc/Hexane (0 to 50%)

Sources & evidence

ORD record
ord-e1c5142f8439444a8b44d0f1018906d2
Source dataset
uspto-grants-2015_05
Patent number
US09023864B2

Reaction notes

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