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

HRID 2355488Notes

Reaction equation

HRID 2355488 reaction equation
[OH:1][C:2]1([CH2:8][CH:9]([NH2:22])[CH2:10][N:11]([CH3:21])[C:12](=[O:20])[O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[Si](Cl)(C)(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:22][CH:9]([CH2:8][C:2]3([OH:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]3)[CH2:10][N:11]([CH3:21])[C:12]([O:13][CH2:14][CH2:15][Si:16]([CH3:17])([CH3:19])[CH3:18])=[O:20])=[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 67189342HCID 67189342, compoundHCID 67191599(S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride

Product 1

HCID 67190261(3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamideYield 54.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of (2-(trimethylsilyl)ethyl 3-(1-hydroxycyclohexyl)-2-aminopropylmethylcarbamate (18.3 mg, 0.055 mmol) in CH2Cl2 (2 mL) were added Et3N (0.2 mL) and Me3SiCl (12 mg, 14 μL, 0.11 mmol). The resulting solution was stirred for 1 h and evaporated under vacuum. The residue was dissolved in CH2Cl2 (2 mL), then pyridine (0.05 mL) was added, followed by 4-nitrophenyl chloroformate (13.5 mg, 0.66 mmol). The mixture was stirred for 30 min and (S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol hydrochloride (19 mg, 0.055 mmol) was added. The mixture was stirred for 10 min and evaporated. The residue was purified by prep HPLC to give (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N-(3-(1-hydroxycyclohexyl)-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide (20 mg, 54%). MS m/z 668 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-1913184e6f87481eb467e9638d15a493
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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