Diisopropylamine → HCID 117698034, compound

HRID 1778535Notes

Reaction equation

HRID 1778535 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][C:14](=[O:18])[O:15][CH2:16][CH3:17].[CH2:19]([N:26]1[CH:31]2[C:32]([F:35])([F:34])[CH2:33][CH:27]1[CH2:28][C:29](=[O:36])[CH2:30]2)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1.CN1C(=O)CCC1.C1COCC1>[CH2:19]([N:26]1[CH:31]2[C:32]([F:35])([F:34])[CH2:33][CH:27]1[CH2:28][C:29]([CH2:13][C:14]([O:15][CH2:16][CH3:17])=[O:18])([OH:36])[CH2:30]2)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 117698128HCID 117698128, compoundHCID 178418339Butyllithium

Product 1

HCID 117698034HCID 117698034, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22156051tetrahydrofuran N-methylpyrrolidinoneSolvent

Procedure

To a solution of diisopropylamine (1.02 g, 10 mmol, 5.0 eq) in THF (10 mL) was added n-BuLi (5 mL, 2.0 M, 5.0 eq) dropwise at −50° C. After 30 min, dry EA (880 mg, 10 mmol, 5.0 eq) in NMP/THF (11 mL, 1:10) was added dropwise. After 1 h at −50° C., a solution of compound 116h (500 mg, 2 mmol, 1.0 eq) in THF (5 mL) was added slowly, and the resulting mixture was warmed from −50° C. to room temperature for 2 h. The reaction mixture was quenched with water (50 mL), extracted with EA (100 mL). The organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel (EA/PE=1:3) to give ethyl 2-(8-benzyl-6,6-difluoro-3-hydroxy-8-azabicyclo[3.2.1]octan-3-yl)acetate 116i as a colorless oil. 490 mg, yield: 72%. 1H NMR (400 MHz, DMSO-d6) ppm 7.37-7.19 (m, 5H), 4.45 (s, 1H), 4.09 (q, J=7.0 Hz, 2H), 3.84-3.70 (m, 2H), 3.27 (d, J=5.0 Hz, 1H), 3.08 (d, J=11.3 Hz, 1H), 2.70 (q, J=13.6 Hz, 1H), 2.43 (s, 2H), 2.37-2.26 (m, 1H), 2.13-2.00 (m, 2H), 1.84-1.72 (m, 1H), 1.52 (d, J=14.3 Hz, 1H), 1.22 (t, J=7.0 Hz, 3H); MS: calc'd (MH+) 340, measured (MH+) 340.

Workup

  1. waitAfter 1 h at −50° C.
  2. temperaturethe resulting mixture was warmed from −50° C. to room temperature for 2 h
  3. customThe reaction mixture was quenched with water (50 mL)
  4. extractionextracted with EA (100 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel (EA/PE=1:3)

Sources & evidence

ORD record
ord-0479430b61084aa38566e0527c01ecea
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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