Potassium Carbonate → Ethyl 5-{(tert-butoxycarbonyl)[2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

HRID 875323Notes

Reaction equation

HRID 875323 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[OH:32])[CH:9]1[CH2:18][CH2:17][CH2:16][C:15]2[N:14]=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:12]=[CH:11][C:10]1=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:46]=[CH:45][C:44]([C:47]([F:50])([F:49])[F:48])=[CH:43][CH:42]=2)=[CH:37][C:36]=1[Cl:51].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[O:32][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]2[CH:42]=[CH:43][C:44]([C:47]([F:48])([F:50])[F:49])=[CH:45][CH:46]=2)=[CH:37][C:36]=1[Cl:51])[CH:9]1[CH2:18][CH2:17][CH2:16][C:15]2[N:14]=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH:12]=[CH:11][C:10]1=2)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86709811Ethyl 5-{(tert-butoxycarbonyl)[2-(2-hydroxyphenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylateHCID 867098134-(Bromomethyl)-3-chloro-4'-(trifluoromethyl)biphenyl

Product 1

HCID 86709812Ethyl 5-{(tert-butoxycarbonyl)[2-(2-{[3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}-phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 51.21 g (116.24 mmol) of ethyl 5-{(tert-butoxycarbonyl)[2-(2-hydroxyphenyl)-ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate (Enantiomer 2, Example 69A), 44.70 g (127.86 mmol) of 4-(bromomethyl)-3-chloro-4′-(trifluoromethyl)biphenyl and 40.16 g (290.60 mmol) of potassium carbonate in 1420 ml of acetonitrile was heated to 110° C. and stirred at this temperature overnight. After cooling, the reaction mixture was filtered, the filter cake was washed repeatedly with acetonitrile and the combined filtrates were concentrated to dryness on a rotary evaporator. The residue obtained was purified chromatographically on silica gel (2.5 kg) (mobile phase: petroleum ether/ethyl acetate 4:1). This gave 79 g (111.39 mmol, 96% of theory) of the target compound.

Workup

  1. temperatureAfter cooling
  2. filtrationthe reaction mixture was filtered
  3. washthe filter cake was washed repeatedly with acetonitrile
  4. concentrationthe combined filtrates were concentrated to dryness on a rotary evaporator
  5. customThe residue obtained
  6. customwas purified chromatographically on silica gel (2.5 kg) (mobile phase: petroleum ether/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-e86d92df36064e1dac432985bc557b9a
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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