Pyridine → cis-4-benzyloxycarbonylamino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

HRID 369913Notes

Reaction equation

HRID 369913 reaction equation
[CH2:1]([O:8][C:9](=[O:27])[NH:10][C@H:11]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21]([F:24])([F:23])[F:22])[CH:19]=2)[NH:14][C@@H:13]([CH2:25][CH3:26])[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:35]([O:37][CH2:38][CH3:39])=[O:36].[OH-].[K+]>ClCCl>[CH2:38]([O:37][C:35]([N:14]1[C:15]2[C:20](=[CH:19][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:17][CH:16]=2)[C@H:11]([NH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:27])[CH2:12][C@@H:13]1[CH2:25][CH3:26])=[O:36])[CH3:39]

Participants

6

Reactant 4

HCID 1049PyridineHCID 10928Ethyl chloroformateHCID 14797Potassium HydroxideHCID 69581246HCID 69581246, compound

Product 1

HCID 69578494cis-4-benzyloxycarbonylamino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl esterYield 90.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of cis-(2-ethyl-6-trifluoromethyl-1,2,3,4-tetrahydro-quinolin4-yl)-carbamic acid benzyl ester (Example 3B) (37.0 g, 97.9 mmol) and pyridine (23.2 g, 293.7 mmol) in dichloromethane (1 L) was cooled in an ice/water bath as ethyl chloroformate (37.2 g, 342.6 mmol) was added slowly. After stirring at room temperature overnight, the mixture was cooled with an ice/water bath as a 1M potassium hydroxide solution was added to quench the reaction. The organic phase was washed twice with a 2M hydrochloric acid solution, dried over magnesium sulfate, filtered and concentrated in vacuo to afford the crude product which was purified by silica gel chromatography using 10-15% ethyl acetate/hexanes as eluent to afford 40 g of the title product. 1H NMR (CDCl3) δ 0.83 (t, 3H), 1.28 (t, 3H), 1.4-1.6 (m, 3H), 2.53 (m, 1H), 4.23 (m, 2H), 4.47 (m, 1H), 4.80 (m, 1H), 4.94 (m, 1H), 5.18 (s, 2H), 7.3-7.6 (m, 8H).

Workup

  1. additionwas added slowly
  2. additionwas added
  3. customto quench
  4. customthe reaction
  5. washThe organic phase was washed twice with a 2M hydrochloric acid solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford the crude product which
  10. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-2c8e3285d3fb4d31970ac50f05a0151e
Source dataset
uspto-grants-2000_10
Patent number
US06140343

Reaction notes

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