Diisopropylamine → HCID 19906419, compound

HRID 2371810Notes

Reaction equation

HRID 2371810 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]([F:28])([F:27])[C:15]([NH:17][C:18]1[CH:26]=[C:25]2[C:21]([CH2:22][CH:23]=[CH:24]2)=[CH:20][CH:19]=1)=[O:16].Br[CH2:30][C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][C:32]=1[O:41][CH3:42].[Cl-].[NH4+]>CCCCCC.O1CCCC1.C(OCC)(=O)C>[CH3:42][O:41][C:32]1[CH:33]=[C:34]([CH:39]=[CH:40][C:31]=1[CH2:30][C:24]1[C:25]2[C:21](=[CH:20][CH:19]=[C:18]([NH:17][C:15](=[O:16])[C:14]([F:27])([F:28])[F:13])[CH:26]=2)[CH2:22][CH:23]=1)[C:35]([O:37][CH3:38])=[O:36]

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 2759828Methyl 4-(bromomethyl)-3-methoxybenzoateHCID 19906414HCID 19906414, compoundHCID 178418339Butyllithium

Product 1

HCID 19906419HCID 19906419, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-100 °C

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. stirringstirred for 1 h
  2. temperatureto warm to room temperature
  3. stirringstirred for 18 h
  4. washThe mixture was washed (water, brine)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was recrystallized from 10:1 methylene chloride

Sources & evidence

ORD record
ord-56667ed56ffb426d8ad66674b71efdc8
Source dataset
uspto-grants-1992_03
Patent number
US05095038

Reaction notes

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