Sodium hydride → 1,1-Dimethylethyl 5-(4-iodophenyl)-2-[2-(3-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)ethyl]-3-({[4-(methyloxy)phenyl]methyl}oxy)pentanoate

HRID 2382922Notes

Reaction equation

HRID 2382922 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[CH:5][NH:4][C:3]1=[O:9].[H-].[Na+].[I:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][CH:21]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=2)[CH:22]([CH2:30][CH2:31]OS(C)(=O)=O)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:15][CH:14]=1>CN(C)C=O>[I:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19][CH2:20][CH:21]([O:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=2)[CH:22]([CH2:30][CH2:31][N:4]2[CH:5]=[CH:6][C:7](=[O:8])[N:2]([CH3:1])[C:3]2=[O:9])[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 790663-MethyluracilHCID 578870261,1-Dimethylethyl 5-(4-iodophenyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)-2-{2-[(methylsulfonyl)oxy]ethyl}pentanoate

Product 1

HCID 578870241,1-Dimethylethyl 5-(4-iodophenyl)-2-[2-(3-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)ethyl]-3-({[4-(methyloxy)phenyl]methyl}oxy)pentanoateYield 27.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

3-Methyl-2,4(1H,3H)-pyrimidinedione (0.28 g, 2.2 mmol) was added in one portion to a stirred suspension of sodium hydride (60% suspension in mineral oil; 80 mg, 2.0 mmol) in dimethylformamide (3 mL) at room temperature under nitrogen. The resulting suspension was stirred for 5 min then a solution of 1,1-dimethylethyl 5-(4-iodophenyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)-2-{2-[(methylsulfonyl)oxy]ethyl}pentanoate (1.15 g, 1.86 mmol) in dimethylformamide (3 mL) was added in one portion. The resulting solution was heated at 80° C. for 1 h 45 min then cooled to room temperature. The volatiles were evaporated and the residue partitioned between dichloromethane (50 mL) and water (50 mL). The layers were separated and the organic phase evaporated to dryness. The residue was chromatographed on silica gel (10% methanol:dichloromethane) to give the title compound (0.33 g, 27%) as a yellow oil which was a mixture of diastereomers. LC/MS: 3.87 min; z/e 649, calcd (M+1) 649. 1H NMR (400 MHz: CDCl3): 7.55 (2H), 7.25 (2H), 7.10 (1H), 6.90-6.75 (4H), 5.70 (1H), 4.40 (2H), 3.85-3.60 (6H), 3.75-2.45 (3H), 2.00-1.70 (4H), 1.40 (9H).

Workup

  1. temperaturethen cooled to room temperature
  2. customThe volatiles were evaporated
  3. customthe residue partitioned between dichloromethane (50 mL) and water (50 mL)
  4. customThe layers were separated
  5. customthe organic phase evaporated to dryness
  6. customThe residue was chromatographed on silica gel (10% methanol:dichloromethane)

Sources & evidence

ORD record
ord-67e4575ea58545fa912f23bafc00d607
Source dataset
uspto-grants-2012_09
Patent number
US08263602B2

Reaction notes

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