Acetic Acid → 1-(1,4-Dioxaspiro[4.5]decan-8-yl)indoline

HRID 1922513Notes

Reaction equation

HRID 1922513 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=O)[CH2:13]Cl)[CH2:7][CH2:6][CH2:5]2.CN(C)CCN1[C:28]2[C:23](=CC([N+]([O-])=O)=C[CH:27]=2)CC1.[C:33]([OH:36])(=O)[CH3:34].[BH3-]C#N.[Na+].[OH-:41].[Na+]>CO>[O:41]1[C:23]2([CH2:5][CH2:6][CH:7]([N:8]3[C:9]4[C:4](=[CH:3][CH:2]=[CH:11][CH:10]=4)[CH2:13][CH2:12]3)[CH2:27][CH2:28]2)[O:36][CH2:33][CH2:34]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 573433941-(6-Bromo-3,4-dihydro-1(2H)-quinolinyl)-2-chloroethanoneHCID 58289996HCID 58289996, compound

Product 1

HCID 598070311-(1,4-Dioxaspiro[4.5]decan-8-yl)indolineYield 81%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of compound 1 (2.0 g, 16.78 mmol) and compound 2 (3.15 g, 20.139 mmol) in dry methanol (20 mL) was treated with acetic acid (2.4 mL, 42.00 mmol) followed by NaCNBH3 (1.26 g, 20.14 mmol) at 0° C. The resulting mixture was brought to room temperature and stirred for 3 h. The reaction was basified with 1 N NaOH solution (50 mL) and product was extracted into ethyl acetate (2×50 mL). The combined ethyl acetate layer was washed with brine (25 mL) and dried (Na2SO4). The solvent was evaporated and the crude product was purified by column chromatography (ethyl acetate:hexanes, 1:4) to obtain compound 3 (3.52 g, 81%) as a solid. 1H NMR (CDCl3) δ 7.06-7.02 (m, 2H), 6.59 (t, J=14.7 Hz, 1H), 6.42 (d, J=8.1 Hz, 1H), 3.46 (s, 4H), 3.46-3.35 (m, 3H), 2.93 (t, J=16.5 Hz, 2H), 1.87-1.60 (m, 8H). MS-ESI (m/z, %): 262 (8), 260 (MH+, 100), 120 (28).

Workup

  1. customwas brought to room temperature
  2. extractionwas extracted into ethyl acetate (2×50 mL)
  3. washThe combined ethyl acetate layer was washed with brine (25 mL)
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was evaporated
  6. customthe crude product was purified by column chromatography (ethyl acetate:hexanes, 1:4)

Sources & evidence

ORD record
ord-befe0078bdd34b1d9af7952f7f1b9324
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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