Sodium Iodide → HCID 69494587, compound

HRID 916726Notes

Reaction equation

HRID 916726 reaction equation
[CH:1]1[C:6]([Cl:7])=[CH:5][C:4]2[C@:8]([C:18]([F:21])([F:20])[F:19])([C:13]#[C:14][CH:15]3[CH2:17][CH2:16]3)[O:9][C:10]([NH:12][C:3]=2[CH:2]=1)=[O:11].C([O-])([O-])=O.[K+].[K+].[Na+].[I-].[C:30]([NH:37][CH2:38][CH2:39]Br)([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31].C1OCCOCCOCCOCCOCCOC1.FC(F)(F)C(O)=O>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C(#N)C>[C:33]([O:32][C:30](=[O:31])[NH:37][CH2:38][CH2:39][N:12]1[C:3]2[CH:2]=[CH:1][C:6]([Cl:7])=[CH:5][C:4]=2[C:8]([C:13]#[C:14][CH:15]2[CH2:16][CH2:17]2)([C:18]([F:20])([F:21])[F:19])[O:9][C:10]1=[O:11])([CH3:36])([CH3:35])[CH3:34]

Participants

10

Reactant 6

HCID 5238Sodium IodideHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 64139Efavirenz2×HCID 4103526tert-Butyl N-(2-bromoethyl)carbamate3×

Product 1

HCID 69494587HCID 69494587, compoundYield 6.9%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
125 °C

Procedure

To a solution of 250 mg of efavirenz in 10 mL of anhydrous DMF was added 600 mg of anhydrous K2CO3, 120 mg NaI, 490 mg of 2-(BOC-amino)ethyl bromide and 5 mg of 18-crown-6. The reaction mixture was heated at 125° C. for 2 hours. The reaction mixture was cooled to room temperature, and 1 g of 2-(BOC-amino)ethyl bromide and 20 mg of tetrabutylammonium iodide were added and allowed to stir at room temperature 18 hours. The reaction mixture was analyzed by reverse-phase high performance liquid chromatography (RP-HPLC, C-18 Vydac 218TP54 (4.6 mm×250 mm) using a gradient run with water-acetonitrile mixtures containing 0.1% trifluoroacetic acid (0-100% AcCN-0.1% TFA in 20 minutes). This indicated the formation of product with a substantial amount of efavirenz in the reaction mixture. An additional 1 g of 2-(BOC-amino)ethyl bromide was added, and the reaction mixture was heated at 60° C. for 18 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated, and the residue was purified by preparative RP-HPLC using a gradient run (CH3CN/water containing 0.1% trifluoroacetic acid). The column used was a Rainin C-18 (ODS) 60 Å (21.4×250 mm). The desired fractions were combined, concentrated in the rotary evaporator, and then lyophilized to give 25 mg of the desired product 7 as a white solid (M+Na, 481).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperaturethe reaction mixture was heated at 60° C. for 18 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by preparative RP-HPLC
  7. concentrationconcentrated in the rotary evaporator

Sources & evidence

ORD record
ord-67a9934068fd46f692c932820bae6bfe
Source dataset
uspto-grants-2007_09
Patent number
US07271252B2

Reaction notes

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