Cesium carbonate → t-butyl (R)-2-hydroxy-1-(4-((S)-2-methylbutoxy)phenyl)ethylcarbamate

HRID 454972

Reaction equation

HRID 454972 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]([C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[CH2:9][OH:10])([CH3:4])([CH3:3])[CH3:2].[CH3:19][C@@H:20]([CH2:23][CH3:24])[CH2:21]Br.C([O-])([O-])=O.[Cs+].[Cs+].[NH4+].[Cl-]>CN(C=O)C>[C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:19][C@@H:20]([CH3:21])[CH2:23][CH3:24])=[CH:13][CH:12]=1)[CH2:9][OH:10])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 54641671-Bromo-2-methylbutane, (+)-HCID 67073553(R)-tert-butyl (2-hydroxy-1-(4-hydroxyphenyl)ethyl)carbamate

Product 1

HCID 67073736t-butyl (R)-2-hydroxy-1-(4-((S)-2-methylbutoxy)phenyl)ethylcarbamateYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

[(R)-2-Hydroxy-1-(4-hydroxy-phenyl)-ethyl]-carbamic acid t-butyl ester (10 mmol), (S)-2-methylbutyl bromide (2.60 g, 17 mmol) and Cs2CO3 (7.47 g, 23 mmol) were combined in DMF (50 ml). The reaction mixture was heated at 70° C. overnight. Saturated NH4Cl was added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with brine, then dried over MgSO4, filtered and concentrated to give a white crude solid. The crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes) to afford the title compound (2.09 g, 65% yield of 3 steps) as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.22 (d, J=8.6 Hz, 2H), 6.90 (m, 2H), 5.13 (d, J=6.6 Hz, 1H), 4.73 (br. s., 1H), 3.83 (m, 3H), 3.74 (m, 1 H), 2.39 (br. s., 1H), 1.87 (m, 1H), 1.58 (m, 1H), 1.42 (m, 9H), 1.29 (m, 1H), 1.01 (m, 3H), 0.96 (m, 3H); LCMS (ESI) m/e 324.2 [(M+H), calcd for C18H30NO4 324.4].

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×20 ml)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a white crude solid
  9. customThe crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3b4e5dfac7324f46bce8878a68b4b72c
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Linked notes

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