Pyridine → HCID 86756026, compound

HRID 1937466Notes

Reaction equation

HRID 1937466 reaction equation
C(OC([N:11]1[C:20]2[C:15](=[CH:16][C:17]([C:21]([F:24])([F:23])[F:22])=[CH:18][CH:19]=2)[C@H:14]([N:25]([CH2:30][C:31]2[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[C:33]([C:41]([F:44])([F:43])[F:42])[CH:32]=2)[C:26]([O:28][CH3:29])=[O:27])[CH2:13][C@@H:12]1[CH3:45])=O)C1C=CC=CC=1.N1C=CC=CC=1.Cl[C:53]([O:55][CH:56]([CH3:58])[CH3:57])=[O:54].[OH-].[K+]>ClCCl.C1(C)C=CC=CC=1.O>[CH:56]([O:55][C:53]([N:11]1[C:20]2[C:15](=[CH:16][C:17]([C:21]([F:23])([F:24])[F:22])=[CH:18][CH:19]=2)[C@H:14]([N:25]([CH2:30][C:31]2[CH:36]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:34]=[C:33]([C:41]([F:42])([F:43])[F:44])[CH:32]=2)[C:26]([O:28][CH3:29])=[O:27])[CH2:13][C@@H:12]1[CH3:45])=[O:54])([CH3:58])[CH3:57]

Participants

8

Reactant 4

HCID 1049PyridineHCID 7917Isopropyl chloroformateHCID 14797Potassium HydroxideHCID 86756025HCID 86756025, 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 1 N 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 1 N 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-e3b3a635b9d6433496fcd517987830eb
Source dataset
uspto-grants-2002_05
Patent number
US06395751B1

Reaction notes

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