Potassium Carbonate → Di-tert-butyl (4R)-N-(tert-butoxycarbonyl)-4-[4-(3-fluoropropoxy)benzyl]-D-glutamate

HRID 591294Notes

Reaction equation

HRID 591294 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][CH2:43][F:44]>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][CH2:43][F:44])=[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 128991281-Iodo-3-fluoropropaneHCID 70957029di-tert-butyl (4R)-N-(tert-butoxycarbonyl)-4-(4-hydroxybenzyl)-D-glutamate

Product 1

HCID 70674428Di-tert-butyl (4R)-N-(tert-butoxycarbonyl)-4-[4-(3-fluoropropoxy)benzyl]-D-glutamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To 140 mg (0.30 mmol) of di-tert-butyl (4R)—N-(tert-butoxycarbonyl)-4-(4-hydroxy-benzyl)-D-glutamate in 5 mL N,N-dimethylformamide were added 42 mg (0.3 mmol) of powdered potassium carbonate and 56 mg (0.30 mmol) of 1-iodo-3-fluoropropane (ABCR GmbH, Germany) and the resulting suspension was heated for 2 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. The crude product obtained in this manner was chromatographed on silica gel using a dichloromethane/methanol gradient, and 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-21db3bd9c8204eda8ad6943dd2fd18b5
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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