Triethylamine → (1R)-N-[4-(trifluoromethyl)phenyl]-1,8,8-trimethyl-2,4-dioxobicyclo[3.2.1] octane-3-carboxamide

HRID 349784Notes

Reaction equation

HRID 349784 reaction equation
[CH3:1][C@:2]12[C:9]([CH3:11])([CH3:10])[CH:6]([CH2:7][CH2:8]1)[C:5](=[O:12])[CH2:4][C:3]2=[O:13].C(N(CC)CC)C.[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1>CN(C)C1C=CN=CC=1.ClCCl>[F:21][C:22]([F:32])([F:33])[C:23]1[CH:24]=[CH:25][C:26]([NH:29][C:30]([CH:4]2[C:5](=[O:12])[CH:6]3[C:9]([CH3:10])([CH3:11])[C@@:2]([CH3:1])([CH2:8][CH2:7]3)[C:3]2=[O:13])=[O:31])=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 737684-(Trifluoromethyl)phenyl isocyanateHCID 58805524(1R)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 11717599(1R)-N-[4-(trifluoromethyl)phenyl]-1,8,8-trimethyl-2,4-dioxobicyclo[3.2.1] octane-3-carboxamideYield 91.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled solution of (1R)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.36 g, 2.0 mmole), triethylamine (0.20 g, 2.0 mmole) and 4-(dimethylamino)pyridine (0.24 g, 2.0 mmole) in dry dichloromethane (20 mL) was added a solution of 4-(trifluoromethyl)phenyl isocyanate (0.41 g, 2.2 mmole) in dry dichloromethane (3 mL). The resulting reaction mixture was allowed to stir overnight under a nitrogen atmosphere, during which time it came up to room temperature. The resulting mixture was concentrated on a rotary evaporator and then partitioned between dichloromethane and 2N aqueous HCl. The organic layer was dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to give a yellow oil, which was purified by chromatography on silica gel (15% ethyl acetate/hexane) to yield the title compound as a yellow solid (0.67 g, 91% yield), mp=78–81° C.; MS (−) ESI m/z=366 (M−H)−; [α]-D (25)=+24.2° (c=1, EtOH).

Workup

  1. customThe resulting reaction mixture
  2. customcame up to room temperature
  3. concentrationThe resulting mixture was concentrated on a rotary evaporator
  4. custompartitioned between dichloromethane and 2N aqueous HCl
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated on a rotary evaporator
  7. customto give a yellow oil, which
  8. customwas purified by chromatography on silica gel (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7f302ee622cb43c597e4833fcfd462e6
Source dataset
uspto-grants-2007_02
Patent number
US07179943B2

Reaction notes

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