Diisopropylamine → HCID 67378244, compound

HRID 524406Notes

Reaction equation

HRID 524406 reaction equation
[Li]CCCC.C(NC(C)C)(C)C.[CH2:13]([O:15][C:16](=[O:42])[C:17]([C:20]1[N:21]=[C:22]([N:25]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[S:23][CH:24]=1)([CH3:19])[CH3:18])[CH3:14].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:53])(=O)=O)=CC=1.[NH4+].[Cl-]>C1COCC1>[CH2:13]([O:15][C:16](=[O:42])[C:17]([C:20]1[N:21]=[C:22]([N:25]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[S:23][C:24]=1[F:53])([CH3:19])[CH3:18])[CH3:14]

Participants

7

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 67363725HCID 67363725, compoundHCID 178418339Butyllithium

Product 1

HCID 67378244HCID 67378244, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Under anhydrous condition n-BuLi (3.6 M solution in hexane, 2.55 mL, 9.20 mmol) was added to stirred solution of N,N-Diisopropyl amine (1.29 mL, 9.20 mmol) in 10 mL dry THF at −78° C. and reaction mixture was stirred for 1 hr. A solution of 2-{2-[tert-Butoxycarbonyl-(4-methoxy-benzyl)-amino]-thiazol-4-yl}-2-methyl-propionic acid ethyl ester (synthesized as per preparation 44; 2.0 g, 4.60 mmol) in 10 mL of dry THF was added dropwise to above reaction mixture and continued to stir for an additional 1 hr at −78° C. N-Fluorobenzenesulfonimide (2.17 g, 6.90 mmol) dissolved in 10 mL dry THF was added to reaction mixture dropwise and resulted reaction mixture was allowed to warm 0° C. within 3 hrs. Reaction mixture was poured on aq. saturated solution of NH4Cl (50 mL), mixture was then extracted with (3×50 mL) ethyl acetate; organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and washed with ethyl acetate and solvent was removed under reduced pressure. The crude material was purified by silica-gel column chromatography (4% ethyl acetate in hexane) to afford pure compound (0.5 g).

Workup

  1. customreaction mixture
  2. stirringto stir for an additional 1 hr at −78° C
  3. additionwas added to reaction mixture dropwise
  4. customresulted
  5. customreaction mixture
  6. customReaction mixture
  7. extractionwas then extracted with (3×50 mL) ethyl acetate
  8. washorganic layer was washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. washwashed with ethyl acetate and solvent
  12. customwas removed under reduced pressure
  13. customThe crude material was purified by silica-gel column chromatography (4% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-9d2d6ff8db0947ee9a921b543263256d
Source dataset
uspto-grants-2016_05
Patent number
US09340506B2

Reaction notes

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