N,N,N',N'-Tetramethylethylenediamine → HCID 66638798, compound

HRID 1094465Notes

Reaction equation

HRID 1094465 reaction equation
[C:1]([NH:5][C:6](=[O:18])[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[N:9][C:8]=1[CH3:17])([CH3:4])([CH3:3])[CH3:2].CN(CCN(C)C)C.[Li+].CC([N-]C(C)C)C.[C:35]([O:39][C:40](=[O:58])[NH:41][C@@H:42]([C:52](=[O:57])N(OC)C)[CH2:43][C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=1[F:51])([CH3:38])([CH3:37])[CH3:36].OS([O-])(=O)=O.[Na+]>C1COCC1.O>[C:35]([O:39][C:40](=[O:58])[NH:41][C@H:42]([CH2:43][C:44]1[CH:49]=[C:48]([F:50])[CH:47]=[CH:46][C:45]=1[F:51])[C:52](=[O:57])[CH2:17][C:8]1[C:7]([C:6](=[O:18])[NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:12][CH:11]=[C:10]([C:13]([F:14])([F:15])[F:16])[N:9]=1)([CH3:38])([CH3:36])[CH3:37]

Participants

8

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 516919Sodium BisulfateHCID 2724682Lithium diisopropylamideHCID 32217502HCID 32217502, compoundHCID 59799830HCID 59799830, compound

Product 1

HCID 66638798HCID 66638798, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-68 °C

Procedure

To a solution of N-tert-butyl-2-methyl-6-trifluoromethyl-nicotinamide (2.3 g, 8.7 mmol) and TMEDA (2.7 mL, 17 mmol) in 130 mL of THF at −68° C. is slowly added LDA (2M, 8.7 mL, 17.4 mmol). The reaction temperature is maintained at −68° C., then warmed to −20° C. and is then immediately re-cooled to −68° C. To the reaction is added a solution of [(R)-2-(2,5-difluoro-phenyl)-1-(methoxy-methyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester (1 g, 2.9 mmol) in 20 mL of THF over a period of 10 minutes. The reaction is allowed to stir an additional 20 min after which the reaction is poured into 150 mL of a chilled 3% (w/v) solution of NaHSO4 in water. The solution is adjusted to pH7 by addition of pH7 buffer and the product is extracted into dichloromethane. The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification of the resultant residue by silica gel flash column chromatography provides the title compound.

Workup

  1. customat −68° C.
  2. temperaturewarmed to −20° C.
  3. temperatureis then immediately re-cooled to −68° C
  4. additionThe solution is adjusted to pH7 by addition of pH7 buffer
  5. extractionthe product is extracted into dichloromethane
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the resultant residue by silica gel flash column chromatography

Sources & evidence

ORD record
ord-d8b79bafef0048b7aad0216debba1e85
Source dataset
uspto-grants-2012_03
Patent number
US08133907B2

Reaction notes

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