Sodium cyanoborohydride → 2-(trimethylsilyl)ethyl (2S)-2-((3R)-3-((1R)-(2-aminopropoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

HRID 451919Notes

Reaction equation

HRID 451919 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:38][CH2:39][C:40](=O)[CH3:41])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([NH:17][C@@H:18]([CH2:31][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)[CH2:19][N:20]([CH3:30])[C:21](=[O:29])[O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[BH3-]C#[N:45].[Na+]>CO>[NH2:45][CH:40]([CH3:41])[CH2:39][O:38][C@@H:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]([NH:17][C@@H:18]([CH2:31][CH:32]2[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]2)[CH2:19][N:20]([CH3:30])[C:21](=[O:29])[O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:28])[CH3:27])=[O:16])[CH2:10]1

Participants

4

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 866394602-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(3-chlorophenyl)(2-oxopropoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate

Product 1

HCID 866394612-(trimethylsilyl)ethyl (2S)-2-((3R)-3-((1R)-(2-aminopropoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamateYield 494.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A mixture of 2-(trimethylsilyl)ethyl (S)-2-((R)-3-((R)-(3-chlorophenyl)(2-oxopropoxy)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate (0.0487 g, 0.078 mmol, 1.0 equiv), NaBH3CN (0.0296 g, 0.471 mmol, 6.0 equiv), NH4OAc (0.2550 g, 3.31 mmol, 42 equiv), and 4 A molecular sieves (0.0555 g) in MeOH (1 mL) was stirred at rt for 22 h. The reaction mixture was diluted with MeOH and filtered through filter agent, Celite® 545. The filtrate was evaporated under reduced pressure to afford 0.2405 g of crude 2-(trimethylsilyl)ethyl (2S)-2-((3R)-3-((1R)-(2-aminopropoxy)(3-chlorophenyl)methyl)piperidine-1-carboxamido)-3-cyclohexylpropyl(methyl)carbamate, which was used in the next step without further purification. MS ESI +ve m/z 625 (M+H).

Workup

  1. filtrationfiltered
  2. filtrationthrough filter agent, Celite® 545
  3. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-fecbcbda64e74edf9d9ab3d0d8df635e
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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