Ethyl Acetate → tert-Butyl (3-{cyclopropyl {3-(3-methoxypropyl)-5-[3-(methylthio)propoxy]benzyl}amino)-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

HRID 561874Notes

Reaction equation

HRID 561874 reaction equation
C1([C:4]2([N:7]([CH2:40][C:41]3[CH:46]=[C:45]([CH2:47][CH2:48][CH2:49][O:50][CH3:51])[CH:44]=[C:43]([OH:52])[CH:42]=3)[C:8](=[O:39])[CH:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][C:30]4[C:35]([Cl:36])=[CH:34][C:33]([CH3:37])=[CH:32][C:31]=4[Cl:38])=[CH:22][CH:21]=3)[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:6][CH2:5]2)CC1.CS(O[CH2:58][CH2:59][CH2:60][S:61][CH3:62])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C>[CH:4]1([N:7]([CH2:40][C:41]2[CH:42]=[C:43]([O:52][CH2:58][CH2:59][CH2:60][S:61][CH3:62])[CH:44]=[C:45]([CH2:47][CH2:48][CH2:49][O:50][CH3:51])[CH:46]=2)[C:8](=[O:39])[CH:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][O:29][C:30]3[C:31]([Cl:38])=[CH:32][C:33]([CH3:37])=[CH:34][C:35]=3[Cl:36])=[CH:22][CH:21]=2)[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:16])([CH3:17])[CH3:15])[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 8857Ethyl Acetate2×HCID 10796Cesium carbonateHCID 229318563-(Methylsulfanyl)propyl methanesulfonateHCID 86635933tert-Butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl](cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

Product 1

HCID 86635936tert-Butyl (3-{cyclopropyl {3-(3-methoxypropyl)-5-[3-(methylthio)propoxy]benzyl}amino)-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl](cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate from Example 70, Step 2 (1 eq.) in DMF (0.05 M) was added 3-(methylthio)propyl methanesulfonate from the previous step (1.4 eq.) and cesium carbonate (1.4 eq.). The resulting suspension was heated at 60° C. for 12 h. The reaction mixture was quenched sat. aq. NaHCO3 and then extracted with ether. The combined organic extracts were washed with water and brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 3:2 (v/v) Hex:EtOAc→2:3 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil.

Workup

  1. customThe reaction mixture was quenched sat. aq. NaHCO3
  2. extractionextracted with ether
  3. washThe combined organic extracts were washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo
  7. customPurification of the crude product
  8. customthus obtained by way of flash chromatography (SiO2, 3:2 (v/v)

Sources & evidence

ORD record
ord-da944eeb2ce3424bb3bdd02d9f3acca8
Source dataset
uspto-grants-2011_11
Patent number
US08063105B2

Reaction notes

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