Potassium Phosphate, Tribasic → [3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-acetic acid ethyl ester

HRID 900147Notes

Reaction equation

HRID 900147 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=1)[CH3:2].[CH2:25]([N:32]1[CH2:39][CH2:38][NH:37][CH2:36][C:33]21[CH2:35][CH2:34]2)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]([N:37]2[CH2:36][C:33]3([CH2:35][CH2:34]3)[N:32]([CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:39][CH2:38]2)[CH:7]=1)[CH3:2]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 113900664-Benzyl-4,7-diazaspiro[2.5]octaneHCID 44479436(3-Trifluoromethanesulfonyloxy-naphthalen-1-yl)-acetic acid ethyl ester

Product 1

HCID 68902420[3-(4-Benzyl-4,7-diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

(3-Trifluoromethanesulfonyloxy-naphthalen-1-yl)-acetic acid ethyl ester (500 mg, 1.38 mmol) is dissolved under an atmosphere of argon in dry THF (10 ml). 4-Benzyl-4,7diaza-spiro[2.5]octane (325 mg, 1.61 mmol) is added, followed by the addition of K3PO4 (410 mg, 1.93 mmol), Pd2(dba)3 (62 mg, 0.069 mmol) and biphenyl-2-yl-di-tert-butyl-phosphane (21 mg, 0.069 mmol). The reaction mixture is heated to 80° C. After 4 h, TLC analysis indicates complete consumption of starting materials. The reaction mixture is cooled to RT, filtered and concentrated. The residue is purified by FCC (hexanes/EtOAc 100:0 to 90;10 to 80:20 to 70:30 to 0:100) to afford the title compound. 1H NMR (CDCl3, 400 MHz) δ 0.69 (ddd, 2H), 0.86 (ddd, 2H), 1.24 (t, J=7.0 Hz, 3H), 3.09 (ddd, 2H), 3.19 (s, 2H), 3.31 (ddd, 2H), 3.93 (s, 2H), 4.02 (s, 2H), 4.17 (q, J=7.0 Hz, 2H), 7.08 (s, 1H), 7.21 (s, 1H), 7.33 (m, 6H), 7.42 (dd, J=8.8 Hz, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H); ES-MS: 415 [M+H]+.

Workup

  1. customconsumption of starting materials
  2. temperatureThe reaction mixture is cooled to RT
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by FCC (hexanes/EtOAc 100:0 to 90;10 to 80:20 to 70:30 to 0:100)

Sources & evidence

ORD record
ord-25ab25f9fc954285a7aff43fdc572649
Source dataset
uspto-grants-2008_04
Patent number
US07358253B2

Reaction notes

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