Chlorotrimethylsilane → (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propyl)piperidine-1-carboxamide

HRID 1254374Notes

Reaction equation

HRID 1254374 reaction equation
[NH2:1][CH2:2][CH:3]([N:12]([CH3:22])[C:13]([O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])=[O:14])[CH2:4][C:5]1([OH:11])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.C[Si](Cl)(C)C.Cl[C:29](OC1C=CC([N+]([O-])=O)=CC=1)=[O:30].Cl.[Cl:42][C:43]1[CH:44]=[C:45]([C@:49]([C@@H:57]2[CH2:62][CH2:61][CH2:60][NH:59][CH2:58]2)([OH:56])[CH2:50][CH2:51][CH2:52][CH2:53][O:54][CH3:55])[CH:46]=[CH:47][CH:48]=1>C(Cl)Cl.CCN(CC)CC>[Cl:42][C:43]1[CH:44]=[C:45]([C@:49]([C@@H:57]2[CH2:62][CH2:61][CH2:60][N:59]([C:29]([NH:1][CH2:2][CH:3]([N:12]([CH3:22])[C:13]([O:15][CH2:16][CH2:17][Si:18]([CH3:20])([CH3:19])[CH3:21])=[O:14])[CH2:4][C:5]3([OH:11])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]3)=[O:30])[CH2:58]2)([OH:56])[CH2:50][CH2:51][CH2:52][CH2:53][O:54][CH3:55])[CH:46]=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 821294-Nitrophenyl chloroformateHCID 671900581-(3-amino-2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propyl)cyclohexanolHCID 67191599(S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride

Product 1

HCID 67189715(3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propyl)piperidine-1-carboxamideYield 51.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 1-(3-amino-2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propyl)cyclohexanol (21 mg, 0.064 mmol) in CH2Cl2 (2 mL) was added Et3N (0.2 mL) and TMSCl (13.9 mg, 164, 0.13 mmol). The resulting solution was stirred for 1 h and evaporated under vacuum The residue was dissolved in CH2Cl2 (2 mL) and pyridine (0.05 mL) was added, followed by 4-nitrophenyl chloroformate (15 mg, 0.077 mmol). The solution was stirred for 30 min and (S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride (27 mg, 0.077 mmol) was added. The resulting mixture was stirred for 10 min and evaporated. The residue was purified by preparative HPLC to give (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-2-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propyl)piperidine-1-carboxamide (22 mg, 51%). MS m/z 668 (M+H+).

Workup

  1. customevaporated under vacuum The residue
  2. dissolutionwas dissolved in CH2Cl2 (2 mL)
  3. additionpyridine (0.05 mL) was added
  4. stirringThe solution was stirred for 30 min
  5. stirringThe resulting mixture was stirred for 10 min
  6. customevaporated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-5f3418f6fff84b11ab4568ca56a3ac82
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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