Water → tert-Butyl 4-((1S)-1-{[(benzyloxy)carbonyl]amino}ethyl)benzoate

HRID 1293179Notes

Reaction equation

HRID 1293179 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]1[CH:22]=[CH:21][C:17]([C:18]([OH:20])=[O:19])=[CH:16][CH:15]=1)[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[C:30]([CH3:33])([CH3:32])[CH3:31].O>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CN(C)C(=O)C>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]1[CH:15]=[CH:16][C:17]([C:18]([O:20][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:19])=[CH:21][CH:22]=1)[CH3:13])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10485t-Butyl bromideHCID 11430Potassium CarbonateHCID 575722614-[(1S)-1-[[(Benzyloxy)carbonyl]amino]ethyl]benzoic acid

Product 1

HCID 69048022tert-Butyl 4-((1S)-1-{[(benzyloxy)carbonyl]amino}ethyl)benzoateYield 79%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 4-((1S)-1-{[(benzyloxy)carbonyl]amino}ethyl)benzoic acid (step 1, 3.7 g, 12.4 mmol) and benzyltriethylammonium chloride (3.0 g, 13 mmol) in N,N-dimethylacetamide (100 mL) was added anhydrous potassium carbonate (47 g, 340 mmol) followed by 2-bromo-2-methylpropane (89 g, 650 mmol). The resulting mixture stirred for 24 h at 55° C. After cooling to room temperature, the reaction mixture was poured into cold water (500 mL) under stirring. The resulting solution was extracted with ethyl acetate (500 mL). The organic phase was washed with water (300 mL) and brine (200 mL), dried (sodium sulfate), and evaporated. The residue was purified by flush column chromatography on silica gel (150 g) eluting with hexane/ethyl acetate (3/1) to afford 3.48 g (79%) of the title compounds as white solids: 1H-NMR (CDCl3) δ 7.95 (2H, d, J=8.3 Hz), 7.44–7.24 (7H, m), 5.15–4.99 (3H, m), 4.88 (1H, br.s), 1.58 (9H, s), 1.47 (3H, d, J=7.0 Hz).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringunder stirring
  3. extractionThe resulting solution was extracted with ethyl acetate (500 mL)
  4. washThe organic phase was washed with water (300 mL) and brine (200 mL)
  5. dry with materialdried (sodium sulfate)
  6. customevaporated
  7. customThe residue was purified
  8. customby flush column chromatography on silica gel (150 g)
  9. washeluting with hexane/ethyl acetate (3/1)

Sources & evidence

ORD record
ord-6e9ca82eae894ac081175c7c47b05da5
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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