Triethylamine → HCID 59752243, compound

HRID 750387Notes

Reaction equation

HRID 750387 reaction equation
FC(F)(F)S([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])(=O)=O.O[CH:17]1[C:21]([CH3:23])([CH3:22])[CH2:20][NH:19][C:18]1=[O:24].C(N(CC)CC)C.N12CCCN=C1CCCCC2>ClCCl.CN(C)C1C=CN=CC=1>[Si:7]([O:6][CH:17]1[C:21]([CH3:23])([CH3:22])[CH2:20][NH:19][C:18]1=[O:24])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonate3×HCID 232609223-Hydroxy-4,4-dimethylpyrrolidin-2-one

Product 1

HCID 59752243HCID 59752243, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

tert-Butyldimethylsilyl trifluoromethanesulfonate (0.810 ml, 3.45 mmol) was added to a mixture of 3-hydroxy-4,4-dimethyl-2-pyrrolidinone (405 mg, 3.1 mmol) and triethylamine (0.481 mmol, 3.45 mmol) in anhydrous dichloromethane (20 mL) at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature, and was stirred for 18 h. A catalytic portion of 4-(dimethylamino)pyridine was added, and the mixture was stirred for 5 h. 1,8-Diazabicyclo[5.4.0]undec-7-ene (0.470 mL, 3.13 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate (0.360 ml, 1.61 mmol) were then added. After an additional 16 h, a third portion of tert-butyldimethylsilyl trifluoromethanesulfonate was added (0.360 ml, 1.61 mmol). The reaction mixture was then stirred for a further 7.5 h, before being diluted with dichloromethane (75 mL). It was then washed with two 30 mL portions of 1N hydrochloric acid. The washes were combined and back-extracted with dichloromethane (30 mL). The dichloromethane layers were then combined, washed with saturated aqueous sodium chloride (20 mL), dried over magnesium sulfate, and concentrated to a tan oil. Further purification of this oil by column chromatography on silica gel, eluting with a gradient of 20-50% ethyl acetate in hexane afforded 3-{[tert-butyl(dimethyl)silyl]oxy}-4,4-dimethyl-2-pyrrolidinone as a colorless oil that crystallized upon standing (362 mg, 48%). 1H NMR (300 MHz, DMSO-d6) δ 7.63 (br s, 1H), 3.85 (s, 1H), 2.96-2.84 (m, 2H), 1.08 (s, 3H), 0.92 (s, 3H), 0.91 (s, 9H), 0.13 (s, 3H), 0.10 (s, 3H). ES-LCMS m/z 244 (M+H).

Workup

  1. stirringthe mixture was stirred for 5 h
  2. waitAfter an additional 16 h
  3. stirringThe reaction mixture was then stirred for a further 7.5 h
  4. washIt was then washed with two 30 mL portions of 1N hydrochloric acid
  5. extractionback-extracted with dichloromethane (30 mL)
  6. washwashed with saturated aqueous sodium chloride (20 mL)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated to a tan oil
  9. customFurther purification of this oil by column chromatography on silica gel
  10. washeluting with a gradient of 20-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-e0961842bc22406481fa2fac612129fc
Source dataset
uspto-grants-2008_07
Patent number
US07402606B2

Reaction notes

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