2,6-Di-tert-butylpyridine → Ethyl 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoate

HRID 899462Notes

Reaction equation

HRID 899462 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:11]=[C:12]([C:14]2([C:19]#[N:20])[CH2:18][CH2:17][CH2:16][CH2:15]2)[CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].[C:21]([O:25][C:26]([NH:28][C:29]([CH3:39])([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:30][OH:31])=[O:27])([CH3:24])([CH3:23])[CH3:22].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>ClC(Cl)C.FC(F)(F)S([O-])(=O)=O.[Ag+]>[C:21]([O:25][C:26]([NH:28][C:29]([CH3:39])([CH2:32][C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[CH2:30][O:31][CH2:2][C:3]1[CH:4]=[C:5]([CH:11]=[C:12]([C:14]2([C:19]#[N:20])[CH2:18][CH2:17][CH2:16][CH2:15]2)[CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

6

Reactant 3

HCID 685102,6-Di-tert-butylpyridineHCID 59211906Ethyl 3-(bromomethyl)-5-(1-cyanocyclopentyl)benzoateHCID 59694437tert-butyl N-(2-benzyl-1-hydroxypropan-2-yl)carbamate

Product 1

HCID 67319292Ethyl 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoate

Reagents, catalysts & solvents 2

HCID 76223Silver(I) trifluoromethanesulfonateCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of ethyl 3-(bromomethyl)-5-(1-cyanocyclopentyl)benzoate (0.15 g, 0.45 mmol) and 2-tert-butoxycarbonylamino-2-methyl-3-phenylpropan-1-ol (0.21 g, 0.79 mmol in 8 mL dichloroethane was added 2,6-di-tert-butylpyridine, polymer bound (0.72 g, 1.3 mmol) and silver trifluoromethanesulfonate (0.20 g, 0.79 mmol). The reaction was stirred at rt overnight and filtered. Concentration and flash chromatography (silica gel, 0-25% EtOAc/hexanes) gave ethyl 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoate. 1H NMR (400 MHz, CDCl3) δ 8.03 (app d, J=1.5 Hz, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 7.28-7.22 (m, 3H), 7.17 (m, 2H), 4.60 (s, 2H), 4.57 (s, 1H), 4.40 (q, J=7.1 Hz, 2H), 3.55 (d, J=8.9 Hz, 1H), 3.45 (d, J=9.0 Hz, 1H), 3.14 (d, J=13.3 Hz, 1H), 2.95 (d, J=13.2 Hz, 1H), 2.52 (m, 2H), 2.13-1.96 (m, 6H), 1.46 (s, 9H), 1.41 (t, J=7.1 Hz, 3H), 1.28 (s, 3H).

Workup

  1. filtrationfiltered
  2. concentrationConcentration and flash chromatography (silica gel, 0-25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1ab8a08e581644c89cd2f1ad11b540c8
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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