Diisopropylethylamine → 2-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(3-chlorophenyl)(2-oxopropoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

HRID 451918Notes

Reaction equation

HRID 451918 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]([C@@H:14]2[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]2)[O:9][CH2:10][C:11](=[O:13])[CH3:12])[CH:5]=[CH:6][CH:7]=1.[CH:20]1([CH2:26][C@H:27]([NH:40][C:41](=O)[O:42]C2C=CC([N+]([O-])=O)=CC=2)[CH2:28][N:29]([CH3:39])[C:30]([O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])=[O:31])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:9][CH2:10][C:11](=[O:13])[CH3:12])[C@@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([C:41]([NH:40][C@@H:27]([CH2:26][CH:20]3[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]3)[CH2:28][N:29]([CH3:39])[C:30](=[O:31])[O:32][CH2:33][CH2:34][Si:35]([CH3:37])([CH3:38])[CH3:36])=[O:42])[CH2:15]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 592017501-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)propan-2-oneHCID 59382919(S)-4-nitrophenyl 1-cyclohexyl-3-(methyl((2-(trimethylsilyl)ethoxy)carbonyl)amino)propan-2-ylcarbamate

Product 1

HCID 866394602-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(3-chlorophenyl)(2-oxopropoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamateYield 11.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)propan-2-one, obtained as described above, (S)-4-nitrophenyl 1-cyclohexyl-3-(methyl((2-(trimethylsilyl)ethoxy)carbonyl)amino)propan-2-ylcarbamate (0.390 g, 0.81 mmol), and DIPEA (2.5 mL) in CH2Cl2 was stirred at rt for 16 h. After the reaction mixture was evaporated under reduced pressure, the crude product was purified by reversed-phase HPLC to afford 0.0487 g (11.4% in three steps) of 2-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(3-chlorophenyl)(2-oxopropoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate. MS ESI +ve m/z 624 (M+H).

Workup

  1. customobtained
  2. customAfter the reaction mixture was evaporated under reduced pressure
  3. customthe crude product was purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-84281c0fb28c46e6b32422a6ed6c57bc
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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