Diisopropylamine → HCID 178469143, compound

HRID 542138

Reaction equation

HRID 542138 reaction equation
C(NC(C)C)(C)C.[Li][CH2:9]CCC.[NH2:13]/[C:14](/[C:25]([F:28])([F:27])[F:26])=[C:15](/[C:21](=[O:24])[CH2:22][CH3:23])\[C:16]([O:18][CH2:19][CH3:20])=[O:17].[Cl:29][C:30]([F:37])([F:36])C(OCC)=O>CCOCC>[Cl:29][C:30]([F:37])([F:36])[C:23]1[N:13]=[C:14]([C:25]([F:26])([F:27])[F:28])[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:21]([OH:24])[C:22]=1[CH3:9]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 67843Acetic acid, 2-chloro-2,2-difluoro-, ethyl esterHCID 178418339ButyllithiumHCID 178472209HCID 178472209, compound

Product 1

HCID 178469143HCID 178469143, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

To 85 ml of dry ether and 21.4 ml (0.152 mol) of diisopropylamine at -78° C. was added 97 ml (0.150 mol) of 1.55M n-BuLi. After stirring at -78° C. for 20 minutes a solution of 16.3 g (0.068 mol) of product of Example 34 in 10 ml of dry ether was added. After stirring at -78° C. for 1 hour, 35 g (0.221 mol) of ethyl chlorodifluoroacetate was added. Stirring at -78° C. was continued for 1 hour and then warmed to room temperature in 11/2 hour. The reaction mixture was poured into 200 ml of ice water and extracted with ether. The ether was extracted with 15% K2CO3 and water. The water extracts were combined, acidified with concentrated HCl and extracted with ether. The original aqueous layer was acidified with concentrated HCl, extracted with ether and combined with the above ether extract, dried (MgSO4) and concentrated in vacuo affording 17.7 g of solid. This solid was heated on the kugelrohr apparatus at 125° C. for 1/2 hour at atm. pressure and then distilled at 19 Pa, pot temperature 69° C. to give 13.57 g (59.8%) of product as a white solid; mp 37°-39° C.

Workup

  1. additionwas added
  2. stirringStirring at -78° C.
  3. waitwas continued for 1 hour
  4. temperaturewarmed to room temperature in 11/2 hour
  5. extractionextracted with ether
  6. extractionThe ether was extracted with 15% K2CO3 and water
  7. extractionextracted with ether
  8. extractionextracted with ether
  9. extractionextract
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-884d5052cf714f31b3264affaf58a8df
Source dataset
uspto-grants-1987_04
Patent number
US04655816

Linked notes

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