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

HRID 349787Notes

Reaction equation

HRID 349787 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]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[O:30])=[CH:24][C:23]=1[C:31]([F:34])([F:33])[F:32].Cl>CN(C)C1C=CN=CC=1.ClCCl>[F:33][C:31]([F:32])([F:34])[C:23]1[CH:24]=[C:25]([NH:28][C:29]([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:30])[CH:26]=[CH:27][C:22]=1[F:21]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27333834-Fluoro-3-(trifluoromethyl)phenyl isocyanateHCID 58805524(1R)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 11653887(1R)-N-[3(trifluoromethyl)-4-fluorophenyl]-1,8,8-trimethyl-2,4-dioxobicyclo [3.2.1]octane-3-carboxamide

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 (0.18 g, 1.0 mmole), triethylamine (0.10 g, 1.0 mmole) and 4-(dimethylamino)pyridine (0.12 g, 1.0 mmole) in dry dichloromethane (25 mL) was added a solution of 4-fluoro-3-(trifluoromethyl)phenyl isocyanate (0.21 g, 1.0 mmole) in dry dichloromethane (5 mL). The resulting reaction mixture was allowed to stir overnight under a nitrogen atmosphere, during which time it came up to room temperature. It was then stirred at 30° C. for twenty-four hours. The resulting mixture was treated with 2N aqueous HCl (30 mL) and the layers were separated. The aqueous layer was extracted with two additional portions of dichloromethane (50 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator. The desired product was isolated by chromatography on silica gel (10% ethyl acetate/hexane) and recrystallized from 95% ethanol to yield the title compound as a beige solid (0.18 g, 48% yield), mp=96–98° C.; MS (−) ESI m/z=384 (M−H)−; [α]D25=+22.1° (c=1, EtOH).

Workup

  1. customThe resulting reaction mixture
  2. customcame up to room temperature
  3. stirringIt was then stirred at 30° C. for twenty-four hours
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with two additional portions of dichloromethane (50 mL)
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record
ord-45f0468b09374c209663dca08aa6fc46
Source dataset
uspto-grants-2007_02
Patent number
US07179943B2

Reaction notes

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