Methyl iodide → HCID 59468908, compound

HRID 1717203Notes

Reaction equation

HRID 1717203 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@:19]([CH2:32][OH:33])([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1.[CH3:34]I.[H-].[Na+]>CN(C=O)C.FC1C=CC=CC=1COC1C=CC([C@@H]2N(C(OC(C)(C)C)=O)[C@](CO)(C(OC)=O)CC2)=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@:19]([CH2:32][O:33][CH3:34])([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 59468955HCID 59468955, compound

Product 1

HCID 59468908HCID 59468908, compoundYield 109.7%

Reagents, catalysts & solvents 2

HCID 59468955HCID 59468955, compoundCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate (D66, 480 mg, 1.04 mmol) and methyl iodide (130 μl, 2 mmol) in dry DMF (5 ml) at 0° C. was added sodium hydride (60 mg, 1.5 mmol, 60% dispersion in mineral oil) and the mixture was stirred for 1.5 h from 0° C. to r.t. A second batch of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-(hydroxymethyl)-1,2-pyrrolidinedicarboxylate (D62, 46 mg, 0.1 mmol) was dissolved in dry DMF (0.5 ml) and methyl iodide was added. The mixture was cooled at 0° C. and sodium hydride (6 mg, 0.15 mmol, 60% dispersion in mineral oil) was added and the mixture was stirred for 1.5 h from 0° C. to r.t. The reactions were quenched with brine/ice and the two mixtures were combined and extracted with ethyl acetate. The organic layer was washed three times with ice cold brine, dried (Na2SO4) and evaporated to afford the title compound as a colourless oil (540 mg); Rt (HPLC): 6.89 min; MS: (ES/+) m/z: 496 [M+Na] C26H32FNO6 requires 473; 1H NMR (400 MHz, CDCl3) δ(ppm): 7.48-7.59 (m, 1H); 7.42-7.48 (m, 2H); 7.28-7.36 (m, 1H); 7.13-7.21 (m, 1H); 7.03-7.13 (m, 1H); 6.89-7.00 (m, 2H); 5.13 and 5.16 (s, s, 2H); 4.94-5.06 and 4.74-4.83 (m, m, 1H); 4.09-4.19 (m, 1H); 3.78-3.96 (m, 1H); 3.83 (s, 3H); 3.41 (s, 3H); 2.44-2.70 (m, 1H); 2.17-2.36 (m, 2H); 1.69-1.87 (m, 1H); 1.11 and 1.40 (s, s, 9H).

Workup

  1. stirringthe mixture was stirred for 1.5 h from 0° C. to r.t
  2. customThe reactions were quenched with brine/ice
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed three times with ice cold brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated

Sources & evidence

ORD record
ord-6af1f59252bf4557b05bb570ab236663
Source dataset
uspto-grants-2010_09
Patent number
US07803833B2

Reaction notes

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