2,6-Di-tert-butylpyridine → Methyl 3-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoate

HRID 899453Notes

Reaction equation

HRID 899453 reaction equation
[CH2:1]([C:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:11])[CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:21][C:22]1[CH:23]=[C:24]([CH:29]=[C:30]([N:32]([S:36]([CH3:39])(=[O:38])=[O:37])[CH2:33][CH2:34][CH3:35])[CH:31]=1)[C:25]([O:27][CH3:28])=[O:26].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>ClCCl.[O-]S(C(F)(F)F)(=O)=O.[Ag+]>[C:15]([O:14][C:13]([NH:12][C:8]([CH3:11])([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:9][O:10][CH2:21][C:22]1[CH:23]=[C:24]([CH:29]=[C:30]([N:32]([S:36]([CH3:39])(=[O:37])=[O:38])[CH2:33][CH2:34][CH3:35])[CH:31]=1)[C:25]([O:27][CH3:28])=[O:26])=[O:19])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 685102,6-Di-tert-butylpyridineHCID 59211887Methyl 3-(bromomethyl)-5-[(methylsulfonyl)(propyl)amino]benzoateHCID 59694437tert-butyl N-(2-benzyl-1-hydroxypropan-2-yl)carbamate

Product 1

HCID 67318237Methyl 3-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoate

Reagents, catalysts & solvents 2

HCID 76223Silver(I) trifluoromethanesulfonateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (1-benzyl-2-hydroxy-1-methylethyl)carbamate (728 mg, 2.75 mmol) and methyl 3-(bromomethyl)-5-[(methylsulfonyl)(propyl)amino]benzoate (500 mg, 1.37 mmol) in dichloromethane (30 mL) were added silver triflate (423 mg, 1.65 mmol) and 2,6-ditertbutylpyridine polymer bound (1.53 g, 2.75 mmol, loading=1.8 mmol N/g resin, Aldrich 37, 782-1). The reaction mixture was stirred at rt in a sealed flask for 16 h. The reaction mixture was filtered on celite, rinsed with dichloromethane and MeOH, concentrated in vacuo and purified by flash chromatography (silica, 0-45% EtOAc/hexanes) to provide methyl 3-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-5-[(methylsulfonyl)(propyl)amino]benzoate as a white foam (intermediate xx). 1H NMR (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.92 (s, 1H), 7.57 (s, 1H), 7.30-7.20 (m, 3H), 7.18-7.7.14 (m, 2H) 4.60 (s, 2H), 4.56 (s, 1H), 3.95 (s, 3H), 3.68 (t, J=6.7 Hz, 2H), 3.57 (A of AB, d, J=8.9 Hz, 1H), 3.47 (B of AB, d, J=8.9 Hz, 1H), 3.15 (A of AB, d, J=13.2 Hz, 1H), 2.94 (B of AB, d, J=13.2 Hz, 1H), 2.90 (s, 3H), 1.55-1.45 (m, 2H), 1.47 (s, 9H), 1.27 (s, 3H), 0.92 (t, J=7.3 Hz, 3H).

Workup

  1. filtrationThe reaction mixture was filtered on celite
  2. washrinsed with dichloromethane and MeOH
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography (silica, 0-45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-47956b76a1bf48dfa03d51c0acaf5f9a
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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