Benzyl Alcohol → HCID 178464365, compound

HRID 1399517Notes

Reaction equation

HRID 1399517 reaction equation
[F:1][C:2]([F:53])([F:52])[C:3]1[CH:4]=[C:5]([CH:13]([N:15]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][C:29]=2[N:38]([CH2:41][C@H:42]2[CH2:47][CH2:46][C@H:45]([CH2:48][C:49]([OH:51])=[O:50])[CH2:44][CH2:43]2)[CH2:39][CH3:40])[C:16]2[N:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][S:25][CH3:26])=[CH:18][N:17]=2)[CH3:14])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:54](O)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1.CCN=C=NCCCN(C)C.Cl.O>ClC(Cl)C.CN(C1C=CN=CC=1)C>[CH2:54]([O:50][C:49](=[O:51])[CH2:48][C@H:45]1[CH2:46][CH2:47][C@H:42]([CH2:41][N:38]([C:29]2[CH:30]=[CH:31][C:32]([C:34]([F:36])([F:37])[F:35])=[CH:33][C:28]=2[CH2:27][N:15]([CH:13]([C:5]2[CH:4]=[C:3]([C:2]([F:1])([F:52])[F:53])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=2)[CH3:14])[C:16]2[N:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][S:25][CH3:26])=[CH:20][N:21]=2)[CH2:39][CH3:40])[CH2:43][CH2:44]1)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178464361HCID 178464361, compound

Product 1

HCID 178464365HCID 178464365, compoundYield 90.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

Under argon atmosphere, a solution of the (S)-isomer-dominant semi-chiral compound (4) of trans-{4-[({2-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-4-(trifluoromethyl)phenyl}(ethyl)amino)methyl]cyclohexyl}acetic acid (744.1 g, 0.95 mol) obtained in Step 2 in anhydrous dichloroethane (11.6 L) was added with benzyl alcohol (113.1 g, 1.05 mol), WSC.HCl (200.5 g, 1.05 mol) and DMAP (11.9 g, 98 mmol) under ice cooling, and the mixture was stirred overnight at room temperature. The reaction mixture was added with water (10 L), and the mixture was extracted with chloroform (19 L, 14 L). The organic layer was washed with saturated brine (12 L), dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure, and the resulting residue was purified by column chromatography (silica gel: 28 g, developing solvent: heptane/ethyl acetate=6/1) to obtain a semi-chiral compound (5) of trans-{4-[({2-[({1-[3,5-bis(trifluoromethyl)phenyl]ethyl}{5-[2-(methylthio)ethoxy]pyrimidin-2-yl}amino)methyl]-4-(trifluoromethyl)phenyl}(ethyl)amino)methyl]cyclohexyl}acetic acid benzyl ester (yellow oil, 745.8 g, yield: 90%).

Workup

  1. extractionthe mixture was extracted with chloroform (19 L, 14 L)
  2. washThe organic layer was washed with saturated brine (12 L)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customthe resulting residue was purified by column chromatography (silica gel: 28 g, developing solvent: heptane/ethyl acetate=6/1)

Sources & evidence

ORD record
ord-1124c763db1049fd96b6edd12b5030c6
Source dataset
uspto-grants-2014_12
Patent number
US08906895B2

Reaction notes

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