Ethane, 2-bromo-1,1-diethoxy- → 1,1-Dimethylethyl N-((1S)-2-phenyl-1-(2-thiazolyl)ethyl)carbamate

HRID 2282811Notes

Reaction equation

HRID 2282811 reaction equation
[NH2:1][C:2](=[S:19])[C@@H:3]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH2:20](OC(OCC)CBr)[CH3:21]>CC(C)=O.Cl.O1CCOCC1>[C:5]1([CH2:4][C@H:3]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:16])([CH3:15])[CH3:17])[C:2]2[S:19][CH:20]=[CH:21][N:1]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 2

HCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 10902004tert-butyl (S)-2-phenyl-1-thiocarbamoylethylcarbamate

Product 1

HCID 117798171,1-Dimethylethyl N-((1S)-2-phenyl-1-(2-thiazolyl)ethyl)carbamateYield 10.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 180AcetoneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of #13 (5.65 g, 20.2 mmol, 1 eq.) in acetone (101 mL, 0.2 M) was added bromoacetaldehyde diethyl acetal (8.76 mL, 58.2 mmol, 2.89 eq.) and 2 drops of 4 M hydrochloric acid in dioxane. The mixture was degassed with nitrogen three times before being heated to reflux. After 2 hours, the reaction was cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and washed with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude orange oil was diluted with ethyl acetate before being concentrated in vacuo onto silica and purified by silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane) and then by reverse phase chromatography (Method A) to give #14 (625 mg, 10%); HPLC (Protocol E): m/z 304.5 [M+H+], 248.9 [(M−2-methylprop-1-ene)+H+], retention time=7.416 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, major rotamer: δ 7.75 (d, J=3.3 Hz, 1H), 7.75 (br d, J=8.6 Hz, 1H), 7.61 (br d, J=3.1 Hz, 1H), 7.25-7.30 (m, 5H), 4.99 (ddd, J=10.5, 8.9, 4.5 Hz, 1H), 3.29-3.36 (m, 1H, assumed; partially obscured by water signal), 2.98 (dd, J=13.8, 10.6 Hz, 1H), 1.31 (s, 9H).

Workup

  1. customThe mixture was degassed with nitrogen three times
  2. temperaturebefore being heated to reflux
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with saturated aqueous sodium bicarbonate solution
  6. washwashed with brine
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionThe resulting crude orange oil was diluted with ethyl acetate
  11. concentrationbefore being concentrated in vacuo onto silica
  12. custompurified by silica gel chromatography (Gradient: 0% to 35% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-68a64e5528f849d49d82c56bd3391b79
Source dataset
uspto-grants-2015_09
Patent number
US09138486B2

Reaction notes

Loading…