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

HRID 454991Notes

Reaction equation

HRID 454991 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][CH:20]([CH2:23][CH2:24][CH3:25])[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][CH:20]([CH3:21])[CH2:23][CH2:24][CH3:25])=[CH:13][CH:12]=1)[CH2:9][OH:10])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 914161-Bromo-2-methylpentaneHCID 67073553(R)-tert-butyl (2-hydroxy-1-(4-hydroxyphenyl)ethyl)carbamate

Product 1

HCID 67433195t-butyl (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamateYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

[(R)-2-Hydroxy-1-(4-hydroxy-phenyl)-ethyl]-carbamic acid t-butyl ester (0.700 g 2.77 mmol), 2-methylpentyl bromide (0.548 g, 3.32 mmol) and Cs2CO3 (1.17 g, 3.59 mmol) were combined in DMF (15 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 (3×10 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 (0.705 g, 76% yield of 2 steps) as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.21 (d, 2H), 6.89 (d, J=8.6 Hz, 2H), 5.18 (d, J=7.1 Hz, 1H), 4.72 (br. s., 1 H), 3.81 (dd, J=9.0, 5.7 Hz, 3H), 3.72 (m, 1H), 3.49 (s, 2H), 2.54 (br. s., 1H), 1.95 (m, 1H), 1.35 (m, 11H), 1.02 (d, J=6.8 Hz, 3H), 0.93 (m, 3H); LCMS (ESI) m/e 338.2 [(M+H), calcd for C19H32NO4 338.5].

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×10 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-02aab3cb0d894213b54d61e85f132504
Source dataset
uspto-grants-2013_07
Patent number
US08497271B2

Reaction notes

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