1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 19906409, compound

HRID 2371811Notes

Reaction equation

HRID 2371811 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([NH:23][C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH:21]=2)[CH2:16][CH:15]=1)[C:6]([O:8][CH3:9])=[O:7].[CH3:30][O:31]C1C=C(C=CC=1CC1C2C(=CC=C(NC(=O)C(F)(F)F)C=2)C=C1)C(OC)=O.N12CCCN=C1CCCCC2>O1CCCC1>[CH3:1][O:2][C:3]1([O:31][CH3:30])[C:12]([CH2:13][C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([NH:23][C:24](=[O:29])[C:25]([F:27])([F:28])[F:26])[CH:21]=3)[CH2:16][CH:15]=2)=[CH:11][CH:10]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH2:4]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 19906418HCID 19906418, compoundHCID 19906419HCID 19906419, compound

Product 1

HCID 19906409HCID 19906409, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of n-butyllithium in hexane (1.4M, 38.82 ml) was added to a -78° C. solution of diisopropylamine (7.85 ml) in tetrahydrofuran (25 ml). After stirring for 15 min, a solution of 6-(trifluoroacetamido)-3H-indene (5.92 g) in tetrahydrofuran (25 ml) was added and stirred for 1 h. The reaction mixture was cooled to -100° C. and a solution of methyl 4-bromomethyl-3-methoxybenzoate (8.44 g) in tetrahydrofuran (35 ml) was added. The mixture was allowed to warm to room temperature and stirred for 18 h. The reaction mixture was added to saturated ammonium chloride (100 ml) and ethyl acetate (150 ml). The mixture was washed (water, brine), dried (MgSO4) and evaporated. The residue was recrystallized from 10:1 methylene chloride:hexane to give methyl 3-methoxy-4-[6-(trifluoroacetamido)-3H-inden-1-ylmethyl]benzoate (1.48 g, 14%). The residue derived from the filtrate was recrystallized from 3:1 methylene chloride:hexane to give a mixture of methyl 3-methoxy-4-[6-(trifluoroacetamido)-3H-inden-1-ylmethyl]benzoate and methyl 3-methoxy-4-[6-(trifluoroacetamido)-1H-inden-1-ylmethyl]benzoate (1.92 g). This mixture was treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (1.11 g) and tetrahydrofuran (20 ml) for 18 h. After partitioning between ethyl acetate (85 ml) and 1N hydrochloric acid, the organic layer was washed (brine) and dried (MgSO4). Evaporation and trituration with methylene chloride gave a colorless solid. This was combined with the above material to give methyl 3-methoxy-4-[6-(trifluoroacetamido)-3H-inden-1-ylmethyl]-3-methoxybenzoate (2.81 g, 27% total yield from 6-(trifluoroacetamido)-3H-indene); mp 198.5°-200.0° C.; MS(CI), m/e=406(M+H).

Workup

  1. customwas recrystallized from 3:1 methylene chloride
  2. customhexane to give
  3. customAfter partitioning between ethyl acetate (85 ml) and 1N hydrochloric acid
  4. washthe organic layer was washed (brine)
  5. dry with materialdried (MgSO4)
  6. customEvaporation and trituration with methylene chloride
  7. customgave a colorless solid

Sources & evidence

ORD record
ord-4b54b9e3ac154ec7b158921cba6c3a37
Source dataset
uspto-grants-1992_03
Patent number
US05095038

Reaction notes

Loading…