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

HRID 1254203Notes

Reaction equation

HRID 1254203 reaction equation
[CH3:1][Si:2]([CH3:27])([CH3:26])[CH2:3][CH2:4][O:5][C:6]([NH:8][CH2:9][C@@H:10]([NH:18]C(=O)OC(C)(C)C)[CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:7].C(OCC)C.CC1C=CC(S(O)(=O)=O)=CC=1>CCO.CCO.O>[NH2:18][C@@H:10]([CH2:11][CH:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1)[CH2:9][NH:8][C:6](=[O:7])[O:5][CH2:4][CH2:3][Si:2]([CH3:26])([CH3:27])[CH3:1]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 6101p-Toluenesulfonic acidHCID 59382914HCID 59382914, compound

Product 1

HCID 59382944(S)-2-(trimethylsilyl)ethyl 2-amino-3-cyclohexylpropylcarbamateYield 82%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 19096565Water ethanolSolvent

Procedure

(S)-tert-butyl 1-(2-(trimethylsilyl)ethoxycarbonylamino)-3-cyclohexylpropan-2-ylcarbamate (8.5 g, 0.0213 mol) was dissolved into a minimal volume of ethyl ether (120 mL) and added to a solution of tosic acid (4.46 g, 0.023 mol) in 25 mL of absolute EtOH. This solution was placed on a rotary evaporator and ethyl ether 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 solvent. The reaction was completed by 2 h and gave an off-white solid. This material was cooled to rt and dissolved in 100 mL of a mixture EtOH:H2O (1:1, v/v). This was washed with hexanes:EtOAc (5:1, v/v, 3×12 mL), basified with 1N NaOH (pH>10), and extracted with EtOAc (3×50 mL). The combined organic extracts were washed (3×5 mL 1N NaOH, 3×5 mL brine), dried, decanted and stripped to give the free base of (S)-2-(trimethylsilyl)ethyl 2-amino-3-cyclohexylpropylcarbamate (5.24 g, 82%).

Workup

  1. customThis solution was placed on a rotary evaporator and ethyl ether
  2. customwas 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 solvent
  5. customgave an off-white solid
  6. washThis was washed with hexanes:EtOAc (5:1, v/v, 3×12 mL)
  7. extractionextracted with EtOAc (3×50 mL)
  8. washThe combined organic extracts were washed (3×5 mL 1N NaOH, 3×5 mL brine)
  9. customdried
  10. customdecanted

Sources & evidence

ORD record
ord-690401c2e10a48f6a8f36a4a19b7bd64
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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