Potassium Carbonate → Ethyl 5-{(tert-butoxycarbonyl)[2-(2-{[4-(5-chloro-1,3-benzoxazol-2-yl)benzyl]oxy}-5-fluorophenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

HRID 875330Notes

Reaction equation

HRID 875330 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[OH:33])[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].[Cl:34][C:35]1[CH:36]=[CH:37][C:38]2[O:42][C:41]([C:43]3[CH:48]=[CH:47][C:46]([CH2:49]Cl)=[CH:45][CH:44]=3)=[N:40][C:39]=2[CH:51]=1.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]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[O:33][CH2:49][C:46]1[CH:45]=[CH:44][C:43]([C:41]2[O:42][C:38]3[CH:37]=[CH:36][C:35]([Cl:34])=[CH:51][C:39]=3[N:40]=2)=[CH:48][CH:47]=1)[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 289053935-Chloro-2-[4-(chloromethyl)phenyl]-1,3-benzoxazoleHCID 89950552Rac-ethyl 5-{(tert-butoxycarbonyl)[2-(5-fluoro-2-hydroxyphenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

Product 1

HCID 86709819Ethyl 5-{(tert-butoxycarbonyl)[2-(2-{[4-(5-chloro-1,3-benzoxazol-2-yl)benzyl]oxy}-5-fluorophenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4.17 g (9.09 mmol) of rac-ethyl 5-{(tert-butoxycarbonyl)[2-(5-fluoro-2-hydroxyphenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylate, 3.04 g (10.91 mmol) of 5-chloro-2-[4-(chloromethyl)phenyl]-1,3-benzoxazole and 3.14 g (22.74 mmol) of potassium carbonate in 120 ml of acetonitrile were 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 (mobile phase: cyclohexane/ethyl acetate 10:1→4:1). This gave 5.43 g (7.75 mmol, 85% 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 (mobile phase: cyclohexane/ethyl acetate 10:1→4:1)

Sources & evidence

ORD record
ord-f2dccaeb328540daa10a7c76a6323265
Source dataset
uspto-grants-2015_03
Patent number
US08981104B2

Reaction notes

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