Methyl iodide → HCID 59468950, compound

HRID 1717172Notes

Reaction equation

HRID 1717172 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[N:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[C@H:18]([C:27]([O:29][CH3:30])=[O:28])[CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[CH3:32][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[O:29]([C:27]([C@:18]1([CH3:32])[CH2:17][CH2:16][C@H:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:14][CH:13]=2)[N:19]1[C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])=[O:28])[CH3:30]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 59468944HCID 59468944, compound

Product 1

HCID 59468950HCID 59468950, compoundYield 78.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5R)-5-{4-[(phenylmethyl)oxy]phenyl}-1,2-pyrrolidinedicarboxylate (D6, 1.52 g, 3.7 mmol) in dry THF (27 ml) at −78° C. was added LiHMDS (4.0 ml, 4.0 mmol, 1M solution in THF). The mixture was allowed to warm to −20° C. and was stirred for 40 min at that temperature. Then the mixture was again cooled to −78° C. and methyl iodide (3.15 g, 22.1 mmol) was added. The mixture was left stirring for another 30 min at the same temperature. After standard work up, the organic layer was evaporated. The crude material was purified by chromatography on silica gel using cyclohexanes and ethyl acetate (1:0 to 9:1) affording the title compound (1.23 g, 78%); Rt (HPLC): 6.76 min; MS: (ES/+) m/z: 448 [M+Na+]; C25H31NO5 requires 425; 1H NMR (400 MHz, CDCl3) δ(ppm): 7.45-7.38 (m, 4H); 7.35 (t, 2H); 7.29 (t, 1H); 6.90 (d, 2H); 5.04 and 5.01 (s, s, 2H); 4.98 and 4.79 (d, d, 1H); 3.79 (s, 3H); 2.50-2.35 (m, 1H); 2.34-2.22 (m, 1H); 1.87-1.73 (m, 2H); 1.58 and 1.55 (s, s, 3H); 1.37 and 1.09 (s, s, 9H). NOE between the methyl group and the proton at C5 could be observed.

Workup

  1. temperatureThen the mixture was again cooled to −78° C.
  2. waitThe mixture was left
  3. stirringstirring for another 30 min at the same temperature
  4. customAfter standard work up, the organic layer was evaporated
  5. customThe crude material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-ae1f832436794259ae84a503073c6b6e
Source dataset
uspto-grants-2010_09
Patent number
US07803833B2

Reaction notes

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