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

HRID 591293Notes

Reaction equation

HRID 591293 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+].I[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 69804Ethane, 1-fluoro-2-iodo-HCID 70957029di-tert-butyl (4R)-N-(tert-butoxycarbonyl)-4-(4-hydroxybenzyl)-D-glutamate

Product 1

HCID 70674427Di-tert-butyl (4R)-N-(tert-butoxycarbonyl)-4-[4-(2-fluoroethoxy)benzyl]-D-glutamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To 93 mg (0.2 mmol) of di-tert-butyl (4R)—N-(tert-butoxycarbonyl)-4-(4-hydroxybenzyl)-D-glutamate in 4 mL N,N-dimethylformamide were added 56 mg (0.4 mmol) of powdered potassium carbonate and 69.6 mg (0.40 mmol) of 1-iodo-2-fluoroethane and the resulting suspension was heated for 1 h at 100° C. in a microwave oven. 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 (4R)—N-(tert-butoxycarbonyl)-4-[4-(2-fluoroethoxy)benzyl]-D-glutamate was obtained as crude product (40 mg, 39.1%) and deprotected without further purification: 2 mL of trifluoro acetic acid were added to the oily residue and the solution was stirred for 2 d at room temperature. The excess of trifluoro acetic acid was evaporated and the residue was taken up three times in tetrahydrofuran and then 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-233247fed2ad482b9581c5df4d644125
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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