Pyridine → HCID 86756026, compound

HRID 1857493Notes

Reaction equation

HRID 1857493 reaction equation
[CH3:1][O:2][C:3](=[O:35])[N:4]([CH2:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=1)[C@H:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([F:18])([F:17])[F:16])[CH:13]=2)[NH:8][C@@H:7]([CH3:19])[CH2:6]1.N1C=CC=CC=1.Cl[C:43]([O:45][CH:46]([CH3:48])[CH3:47])=[O:44].[OH-].[K+]>ClCCl.C1(C)C=CC=CC=1.O>[CH:46]([O:45][C:43]([N:8]1[C:9]2[C:14](=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[C@H:5]([N:4]([CH2:20][C:21]2[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[C:3]([O:2][CH3:1])=[O:35])[CH2:6][C@@H:7]1[CH3:19])=[O:44])([CH3:48])[CH3:47]

Participants

8

Reactant 4

HCID 1049PyridineHCID 7917Isopropyl chloroformateHCID 14797Potassium HydroxideHCID 86756024HCID 86756024, compound

Product 1

HCID 86756026HCID 86756026, compoundYield 81%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of cis-(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-6-trifluoromethyl-1,2,3,4-tetrahydro-quinolin-4-yl)-carbamic acid methyl ester (Example 70) (95 mg, 0.185 mmol) and anhydrous pyridine (0.5 mL) in anhydrous dichloromethane (2 mL) was added isopropyl chloroformate (1.9 mL of a 1M solution in toluene, 1.85 mmol). After stirring at room temperature overnight, water (5 mL) and an aqueous 10% KOH solution (5 mL) were added, and the mixture was extracted with ethyl acetate (3×10 mL). The combined organic phases were then washed with 1N HCl (3×10 mL), then a saturated sodium bicarbonate solution, and then brine (10 mL of each). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give 117 mg crude product. Purification by silica gel chromatography using 0-10% ethyl acetate/hexanes as eluent afforded 90 mg of the title compound (81%): MS m/z 602 (M+ +2), 619 (M+ +19); 1H NMR (CDCl3) δ 1.20 (Me, d, 3H, J=6.1 Hz), 1.28 (d, 3H), 1.31 (d, 3H), 3.83 (OMe, s, 3H), 5.04 (septet, 1H), 7.12 (C5, s, 1H).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×10 mL)
  2. washThe combined organic phases were then washed with 1N HCl (3×10 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give 117 mg crude product
  7. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-b7169b2cbff844a58a1430db83c90d3e
Source dataset
uspto-grants-2000_11
Patent number
US06147090

Reaction notes

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