Diethyl Ether → 2-(trimethylsilyl)ethyl (S)-2-amino-3-cyclohexylpropylmethylcarbamate

HRID 2355324Notes

Reaction equation

HRID 2355324 reaction equation
[CH:1]1([CH2:7][C@H:8]([NH:21]C(=O)OC(C)(C)C)[CH2:9][N:10]([CH3:20])[C:11]([O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[O:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(OCC)C.CC1C=CC(S(O)(=O)=O)=CC=1>CCO>[NH2:21][C@@H:8]([CH2:7][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[CH2:9][N:10]([CH3:20])[C:11](=[O:12])[O:13][CH2:14][CH2:15][Si:16]([CH3:18])([CH3:19])[CH3:17]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 6101p-Toluenesulfonic acidHCID 59382977(S)-tert-butyl 1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamate

Product 1

HCID 593829982-(trimethylsilyl)ethyl (S)-2-amino-3-cyclohexylpropylmethylcarbamateYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(S)-tert-butyl 1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamate (5.78 g, 0.014 mol) was dissolved into a minimal volume of ethyl ether (100 mL) and added to a solution of TsOH (2.92 g, 0.0154 mol) in 20.0 mL of absolute EtOH. This solution was placed on a rotary evaporator and the Et2O was removed at ambient temp. The flask was then lowered into the water bath (temperature: 60° C.) and the selective de-protection of the BOC group proceeded concurrently with removal of the remainder of the solvent. The reaction was completed by 2 h and gave an off-white solid, which was washed with hexanes:EtOAc (5:1, v/v, 3×10 mL), basified with 1N NaOH (pH>10), and extracted with ethyl ether (3×50 mL). The combined organic extracts were washed with 1N NaOH (3×5 mL) and brine (3×5 mL), dried, decanted and stripped to give the free base of (S)-2-(trimethylsilyl)ethyl 2-amino-3-cyclohexylpropyl(methyl)carbamate (3.5 g, 80%). 1H NMR (400 MHz, CDCl3): 4.15 (t, J=8.4 Hz, 2H), 3.10 (m, 3H), 2.91 (s, 3H), 1.78-1.56 (m, 5H), 1.50-1.00 (M, 6H), 1.00-0.70 (m, 4H), 0.01 (s, 9H). MS (E/Z): 315 (M+H+).

Workup

  1. customThis solution was placed on a rotary evaporator
  2. customthe Et2O was removed at ambient temp
  3. customwas then lowered into the water bath (temperature: 60° C.)
  4. customthe selective de-protection of the BOC group proceeded concurrently with removal of the remainder of the solvent
  5. customgave an off-white solid, which
  6. washwas washed with hexanes:EtOAc (5:1, v/v, 3×10 mL)
  7. extractionextracted with ethyl ether (3×50 mL)
  8. washThe combined organic extracts were washed with 1N NaOH (3×5 mL) and brine (3×5 mL)
  9. customdried
  10. customdecanted

Sources & evidence

ORD record
ord-0ee9143d70ea419d8303e8731075d494
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

Loading…