Triethylamine → [3-Benzyloxy-1(R)-cyanomethyl-propyl]-carbamic acid tert-butyl ester

HRID 564356Notes

Reaction equation

HRID 564356 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][CH:8]([CH2:19]O)[CH2:9][CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([CH3:4])([CH3:3])[CH3:2].S(Cl)(C)(=O)=O.[CH2:27]([N:29](CC)CC)C.[C-]#N.[NH4+].[NH4+].[NH4+].[NH4+].[C-]#N.[C-]#N.[C-]#N>C(Cl)Cl.O>[C:1]([O:5][C:6](=[O:21])[NH:7][C@H:8]([CH2:19][C:27]#[N:29])[CH2:9][CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 21087273tert-Butyl 3-(benzyloxy)-1-(hydroxymethyl)propylcarbamateHCID 86614618Tetraammonium cyanide

Product 1

HCID 67006795[3-Benzyloxy-1(R)-cyanomethyl-propyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

(3-Benzyloxy-1-hydroxymethyl-propyl)-carbamic acid tert-butyl ester (7.4 g, 25 mmole) was dissolved in 100 ml DCM. Mesyl chloride (4.3 g, 37.5 mmole) and triethylamine (5.0 g, 50 mmole) were added. The reaction was stirred at room temperature for 20 minutes. 100 ml DCM and 100 ml water were added. The organic layer washed with brine (100 ml), dried over sodium sulfate and concentrated. The residue was dissolved in 200 ml toluene. Tetraammonium cyanide (10 g, 37.5 mmole) was added and the reaction was stirred at room temperature overnight. The organic layer washed with water (2×100 ml), brine (100 ml), dried over sodium sulfate and concentrated. The residue was purified by column (EtOAc/hexane from 100/0 to 30/70 in 45 minutes). Yield, 6.4 g, 84%. 1H NMR (CDCl3 400 MHz δ 7.29-7.38 (m, 5H), 5.20 (d, J=5.9 Hz, 1H), 4.50 (m, 2H), 3.91 (m, 1H), 3.54-3.66 (m, 2H), 2.60-2.77 (m, 2H), 1.89-1.99 (m, 2H), 1.44 (s, 9H).

Workup

  1. washThe organic layer washed with brine (100 ml)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in 200 ml toluene
  5. stirringthe reaction was stirred at room temperature overnight
  6. washThe organic layer washed with water (2×100 ml), brine (100 ml)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by column (EtOAc/hexane from 100/0 to 30/70 in 45 minutes)
  10. customYield

Sources & evidence

ORD record
ord-6f847be5cb2a4ed29c140f77d569ca54
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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