Hydrochloric Acid → HCID 11653237, compound

HRID 349776Notes

Reaction equation

HRID 349776 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:23]=[C:24]([N:29]=[C:30]=[O:31])[CH:25]=[CH:26][C:27]=1[F:28].Cl>CN(C)C1C=CN=CC=1.ClCCl>[Cl:21][C:22]1[CH:23]=[C:24]([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:25]=[CH:26][C:27]=1[F:28]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27346323-Chloro-4-fluorophenyl isocyanateHCID 58586461(1S)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

Product 1

HCID 11653237HCID 11653237, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

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 3-chloro-4-fluorophenyl isocyanate (0.17 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 seven 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 light orange solid (0.16 g, 47% yield), mp=87–89° C.; MS (−) ESI m/z=352 (M−H)−; [α]D25=−23.1° (c=1, EtOH).

Workup

  1. customThe resulting reaction mixture
  2. customcame up to room temperature
  3. stirringIt was then stirred at 30° C. for seven 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-258a5e4a23834ed7bcdb25850155edc3
Source dataset
uspto-grants-2007_02
Patent number
US07179943B2

Reaction notes

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