Diisopropylamine → HCID 68801861, compound

HRID 2059717Notes

Reaction equation

HRID 2059717 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]1(=[O:26])[C:21]2[CH:20]3[CH2:22][CH2:23][CH2:24][CH2:25][CH:19]3[O:18][C:17]=2[CH2:16][CH2:15][CH2:14]1.[C:27](=O)([O:30]C)[O:28][CH3:29]>O1CCCC1>[O:26]=[C:13]1[C:21]2[CH:20]3[CH2:22][CH2:23][CH2:24][CH2:25][CH:19]3[O:18][C:17]=2[CH2:16][CH2:15][CH:14]1[C:27]([O:28][CH3:29])=[O:30]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 12021Dimethyl CarbonateHCID 15473347HCID 15473347, compoundHCID 178418339Butyllithium

Product 1

HCID 68801861HCID 68801861, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of diisopropylamine (5.56 mL, 39.0 mmol) in tetrahydrofuran (20 mL) was cooled to −78° C. and then treated with n-butyllithium (15.60 mL, 39.0 mmol) added dropwise. The mixture was stirred at this temperature for 30 minutes. The solution was transferred by cannula needle into a solution of the product from Example 1A, (3,4,5a,6,7,8,9,9a-octahydrodibenzo[b,d]furan-1(2H)-one, 2.5 g, 13.00 mmol) in tetrahydrofuran (40 mL) precooled to −78° C., and the resulting mixture was stirred for 30 minutes at −78° C. Then, dimethyl carbonate (11.71 g, 130 mmol) was added and the dry ice bath was removed. The mixture was stirred and allowed to warm to ambient temperature with stirring continued for 16 hours. The mixture was quenched with hydrochloric acid (1N, 40 mL) and diluted with ether (200 mL). The organic layer was separated and the aqueous layer was extracted with additional ether. The organic layers were combined and washed with brine, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with 10-30% ethyl acetate in hexanes to provide the title product: 1H NMR (CDCl3) δ 1.23-1.30 (m, 1H), 1.42-1.56 (m, 3H), 1.72-1.84 (m, 1H), 1.87-2.04 (m, 3H), 2.17-2.26 (m, 1H), 2.31-2.49 (m, 3H), 2.56-2.67 (m, 1H), 3.00-3.10 (m, 1H), 3.32-3.40 (m, 1H), 3.75 (d, J=2.45 Hz, 2H), 4.67-4.75 (m, 1H); MS (DCl/NH3) m/z 251 (M+H)+.

Workup

  1. additionadded dropwise
  2. customprecooled to −78° C.
  3. stirringthe resulting mixture was stirred for 30 minutes at −78° C
  4. customthe dry ice bath was removed
  5. stirringThe mixture was stirred
  6. stirringwith stirring
  7. waitcontinued for 16 hours
  8. customThe mixture was quenched with hydrochloric acid (1N, 40 mL)
  9. additiondiluted with ether (200 mL)
  10. customThe organic layer was separated
  11. extractionthe aqueous layer was extracted with additional ether
  12. washwashed with brine
  13. dry with materialdried with anhydrous magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was chromatographed on silica gel eluting with 10-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-af5022a06d5b4cb18cfbf3b2bc13cc21
Source dataset
uspto-grants-2012_10
Patent number
US08278311B2

Reaction notes

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