3-Chlorobenzoic Acid → HCID 58137248, compound

HRID 1424584Notes

Reaction equation

HRID 1424584 reaction equation
[Li]CCCC.CC1(C)CCCC(C)(C)N1.[Cl:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([OH:22])=[O:21].O=[C:27]1[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1>C1COCC1>[Cl:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:19]2[C:18]=1[C:27]1([CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]1)[O:21][C:20]2=[O:22]

Participants

6

Reactant 4

HCID 4473-Chlorobenzoic AcidHCID 130352,2,6,6-TetramethylpiperidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 58137248HCID 58137248, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

2.5 M n-BuLi in hexanes (9.2 mL, 23 mmol) was added To a stirred solution of 2,2,6,6-tetramethylpiperidine (3.2 g, 23 mmol) in anhydrous THF (30 mL) at −20° C. under N2. The mixture was stirred for 1 h. at −20° C. and then cooled to −78° C. 3-Chlorobenzoic acid (1.8 g, 11.5 mmol) in anhydrous THF (20 mL) was slowly added dropwise and the mixture was stirred for 1 h at −78° C. The mixture was treated with tert-butyl 4-oxopiperidine-1-carboxylate (2.29 g, 11.5 mmol) and the resulting solution was warmed to rt and stirred overnight. The mixture was quenched with water and extracted with EtOAc (3×30 mL). The organic layers were combined, washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product, which was Purified by chromatography to give tert-butyl 7-chloro-3-oxo-3H-spiro[isobenzofuran-1,4′-piperidine]-1′-carboxylate (500 mg, 13%). 1H NMR (CD3OD): δ=1.45 (s, 9H), 2.60 (m, 2H), 3.20 (b, 2H), 4.20 (b, 2H), 7.48 (m, 1H), 7.55 (m, 1H), 7.75 (m, 1H).

Workup

  1. temperaturecooled to −78° C
  2. stirringthe mixture was stirred for 1 h at −78° C
  3. temperaturethe resulting solution was warmed to rt
  4. stirringstirred overnight
  5. customThe mixture was quenched with water
  6. extractionextracted with EtOAc (3×30 mL)
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product, which
  12. customwas Purified by chromatography

Sources & evidence

ORD record
ord-3de26150a36d43cf89ddea95bfe76d41
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

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