2,5-Dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate → (s)-2-(Trimethylsilyl)ethyl 2-(t-butoxycarbonylamino)-3-(1-fluorocyclohexyl)propyl(methyl)carbamate

HRID 451761Notes

Reaction equation

HRID 451761 reaction equation
[F:1][C:2]1([CH2:8][C@H:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:10][NH:11][CH3:12])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[C:21]([O:30]N1C(=O)CCC1=O)([O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])=O>CC#N>[C:16]([O:15][C:14]([NH:13][C@@H:9]([CH2:8][C:2]1([F:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)[CH2:10][N:11]([CH3:12])[C:21](=[O:30])[O:23][CH2:24][CH2:25][Si:26]([CH3:27])([CH3:28])[CH3:29])=[O:20])([CH3:19])([CH3:17])[CH3:18]

Participants

4

Reactant 2

HCID 50183862,5-Dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonateHCID 68710746(S)-tert-butyl 1-(1-fluorocyclohexyl)-3-(methylamino)propan-2-ylcarbamate

Product 1

HCID 59201485(s)-2-(Trimethylsilyl)ethyl 2-(t-butoxycarbonylamino)-3-(1-fluorocyclohexyl)propyl(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Crude (S)-tert-butyl 1-(1-fluorocyclohexyl)-3-(methylamino)propan-2-ylcarbamate and TeocOSu (137 mg, 0.5 mmol) were dissolved in 1:1 CH3CN/10% aqueous K2CO3 (20 mL). The mixture was stirred for 2 h. After this time all of the free amine was consumed. The CH3CN was removed in vacuo and the aqueous residue extracted with EtOAc (3×10 mL). The combine organic extracts washed with brine, dried over Na2SO4, filtered and evaporated. Flash chromatography on silica, eluting with 0-27% EtOAc in hexanes, afforded (S)-2-(trimethylsilyl)ethyl 2-(t-butoxycarbonylamino)-3-(1-fluorocyclohexyl)propyl(methyl)carbamate (70 mg).

Workup

  1. customAfter this time all of the free amine was consumed
  2. customThe CH3CN was removed in vacuo
  3. extractionthe aqueous residue extracted with EtOAc (3×10 mL)
  4. washThe combine organic extracts washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. washFlash chromatography on silica, eluting with 0-27% EtOAc in hexanes

Sources & evidence

ORD record
ord-1a793774ebe146d88833ad98d3e3040a
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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