Potassium Carbonate → Di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-[4-(2-fluoroethoxy)benzyl]-L-glutamate

HRID 591255Notes

Reaction equation

HRID 591255 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:41][CH2:42][F:43]>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:41][CH2:42][F:43])=[CH:22][CH:21]=1)[C:12]([O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 129822-Fluoroethyl bromideHCID 70957078di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-(4-hydroxybenzyl)-L-glutamate

Product 1

HCID 70674315Di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-[4-(2-fluoroethoxy)benzyl]-L-glutamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To 315 mg (0.68 mmol) of di-tert-butyl (4S)—N-(tert-butoxycarbonyl)-4-(4-hydroxy-benzyl)-L-glutamate in 30 mL N,N-dimethylformamide were added 206 mg (1.5 mmol) of powdered potassium carbonate and 104 mg (0.81 mmol) of 1-bromo-2-fluoroethane and the resulting suspension was stirred for 5 h at 60° C. and overnight at room temperature. The reaction mixture was then filtered, the solvent evaporated and the residue was taken up in ethyl acetate and water. The organic phase was separated off, washed with water until neutral, dried over sodium sulfate and filtered, and the filtrate was concentrated in vacuo. Di-tert-butyl (4S)—N-(tert-butoxycarbonyl)-4-[4-(2-fluoroethoxy)benzyl]-L-glutamate was obtained as crude product (110 mg, 32.6%) and deprotected without further purification: 3 mL of trifluoro acetic acid were added to the oily residue and the solution was stirred for 2 days at room temperature. The excess of trifluoro acetic acid was evaporated and the residue was taken up three times in tetrahydrofuran and than evaporated. The resulting oil was chromatographed on C-18 reversed phase silica gel using a water/acetonitrile gradient, the appropriate fractions were combined and concentrated.

Workup

  1. filtrationThe reaction mixture was then filtered
  2. customthe solvent evaporated
  3. customThe organic phase was separated off
  4. washwashed with water until neutral,
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-9260aa57c1bb465fb2a3674f68883e6e
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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