Hydrochloric Acid → HCID 11567560, compound

HRID 349773Notes

Reaction equation

HRID 349773 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.[Cl: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>[Cl:21][C:22]1[CH:27]=[CH:26][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:24][C:23]=1[C:31]([F:32])([F:33])[F:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 58586461(1S)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 11567560HCID 11567560, compoundYield 52.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
30 °C

Procedure

To an ice-cooled solution of (1S)-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-chloro-3-(trifluoromethyl)phenyl isocyanate (0.22 g, 1.0 mmole) in dry dichloromethane (5 mL). The resulting mixture was allowed to stir overnight under a nitrogen atmosphere, during which time it came up to room temperature, and then was heated at 30° C. for 7 hours. The reaction mixture was treated with 2N aqueous HCl and the layers separated. The acidic aqueous layer was extracted with two additional portions of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to give a yellow oil, which was purified by chromatography on silica gel (10% ethyl acetate/hexane) to yield a yellow oil, which was crystallized from 95% ethanol to yield the title compound as an off-white solid (0.21 g, 51% yield), mp=118–120° C.; MS (+) ESI m/z=402 (M+H)+, [α]D25=−23.7° (c=1, EtOH).

Workup

  1. customcame up to room temperature
  2. customthe layers separated
  3. extractionThe acidic aqueous layer was extracted with two additional portions of dichloromethane
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated on a rotary evaporator
  6. customto give a yellow oil, which
  7. customwas purified by chromatography on silica gel (10% ethyl acetate/hexane)
  8. customto yield a yellow oil, which
  9. customwas crystallized from 95% ethanol

Sources & evidence

ORD record
ord-7c14ed457b64445d87c050f9049d4efe
Source dataset
uspto-grants-2007_02
Patent number
US07179943B2

Reaction notes

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