Acetic Acid → 1'-(1,4-dioxaspiro[4.5]decan-8-yl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one

HRID 641192Notes

Reaction equation

HRID 641192 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4]2([O:11][C:10](=[O:12])[NH:9][C:8]3[CH:13]=[CH:14][CH:15]=[CH:16][C:7]2=3)[CH2:3][CH2:2]1.[CH2:17]1[O:27][C:20]2([CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)[O:19][CH2:18]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[O:19]1[C:20]2([CH2:25][CH2:24][CH:23]([N:1]3[CH2:2][CH2:3][C:4]4([O:11][C:10](=[O:12])[NH:9][C:8]5[CH:13]=[CH:14][CH:15]=[CH:16][C:7]4=5)[CH2:5][CH2:6]3)[CH2:22][CH2:21]2)[O:27][CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5049666Sodium triacetoxyborohydrideHCID 13050639Spiro[3,1-benzoxazine-4,4'-piperidin]-2(1H)-one

Product 1

HCID 250609581'-(1,4-dioxaspiro[4.5]decan-8-yl)spiro[benzo[d][1,3]oxazine-4,4'-piperidin]-2(1H)-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Spiro[4H-3,1-benzoxazine-4,4′-piperidin]-2(1H)-one (A4) (400 mg, 1.83 mmol) was suspended in anhydrous 1,2-dichloroethane (8.0 mL) and treated with 1,4-cyclohexanedione mono-ethylene ketal (viia) (429 mg, 2.75 mmol), glacial acetic acid (220 mg, 3.66 mmol), and sodium triacetoxyborohydride (776 mg, 3.66 mmol). The reaction flask was flushed with nitrogen and stirred for 60 hours at room temperature. The reaction was diluted with dichloromethane (25 mL), quenched with 1.0 N NaOH (10 mL), and stirred at room temperature vigorously for 30 minutes. The layers were separated and the aqueous layer was extracted once with dichloromethane (10 mL). The pooled organic layers were washed with water (1×25 mL) and saturated brine (1×25 mL), dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to afford crude 1′-(1,4-dioxaspiro[4.5]decan-8-yl)spiro[benzo[d][1,3]oxazine-4,4′-piperidin]-2(1H)-one (viiib) as a white solid. LC/MS m/z 359.2 [M+H]+, retention time 1.61 min (RP-C18, 10-99% CH3CN/0.05% TFA).

Workup

  1. customThe reaction flask was flushed with nitrogen
  2. additionThe reaction was diluted with dichloromethane (25 mL)
  3. customquenched with 1.0 N NaOH (10 mL)
  4. stirringstirred at room temperature vigorously for 30 minutes
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted once with dichloromethane (10 mL)
  7. washThe pooled organic layers were washed with water (1×25 mL) and saturated brine (1×25 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-f6886954a43f43e2ae10cc0e8333a936
Source dataset
uspto-grants-2010_04
Patent number
US07696201B2

Reaction notes

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