Hexamethylphosphoramide → HCID 68579426, compound

HRID 1665432Notes

Reaction equation

HRID 1665432 reaction equation
C([N-]C(C)C)(C)C.[Li+].[Si:9]([O:16][CH2:17][CH:18]1[CH2:22][N:21]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=2[O:32][CH3:33])[C:20](=[O:34])[CH2:19]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].CN(C)P(N(C)C)(N(C)C)=O.I[CH2:47][C:48]#[C:49][CH2:50][CH2:51][CH2:52][C:53]([O:55][CH3:56])=[O:54]>C1COCC1>[CH3:56][O:55][C:53](=[O:54])[CH2:52][CH2:51][CH2:50][C:49]#[C:48][CH2:47][C@@H:19]1[C@@H:18]([CH2:17][O:16][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[CH2:22][N:21]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=2[O:32][CH3:33])[C:20]1=[O:34]

Participants

6

Reactant 4

HCID 12679HexamethylphosphoramideHCID 2724682Lithium diisopropylamideHCID 10901527Methyl 7-iodohept-5-ynoateHCID 67438743HCID 67438743, compound

Product 1

HCID 68579426HCID 68579426, compoundYield 16.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Lithium diisopropylamide (1.5 M in cyclohexane, 9.22 mL, 13.83 mmol) was added to a solution of 4-(tert-butyldimethylsilanyloxymethyl)-1-(2,4-dimethoxybenzyl)-pyrrolidin-2-one (2.63 g, 6.93 mmol) in THF (41 mL) at −78° C. under nitrogen. After 30 min at −78° C., hexamethylphosphoramide (3.61 mL, 20.7 mmol) was added dropwise. After 30 min at −78° C., methyl 7-iodohept-5-ynoate (5.52 g, 20.7 mmol) in THF (20 mL+3 mL) was added. The reaction mixture was allowed to warm to room temperature. After 18 h at room temperature, the reaction was quenched with saturated aqueous NH4Cl and extracted with EtOAc (3×50 mL). Combined extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by flash column chromatography on silica gel (40% EtOAc/hexane) to afford 579 mg (16%) of 7-[(3R*,4R*)-4-(tert-butyldimethylsilanyloxymethyl)-1-(2,4-dimethoxybenzyl)-2-oxo-pyrrolidin-3-yl]-hept-5-ynoic acid methyl ester.

Workup

  1. waitAfter 30 min at −78° C.
  2. waitAfter 18 h at room temperature
  3. customthe reaction was quenched with saturated aqueous NH4Cl
  4. extractionextracted with EtOAc (3×50 mL)
  5. dry with materialCombined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by flash column chromatography on silica gel (40% EtOAc/hexane)

Sources & evidence

ORD record
ord-fa21f5ad62484d44860741e528908a84
Source dataset
uspto-grants-2011_10
Patent number
US08039507B2

Reaction notes

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