Sodium Bicarbonate → Ethyl 8-fluoro-1,4-dioxaspiro[4.5]decane-8-carboxylate

HRID 75722Notes

Reaction equation

HRID 75722 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:26]N(S(C1C=CC=CC=1)(=O)=O)S(C1C=CC=CC=1)(=O)=O.C([O-])(O)=O.[Na+]>C1COCC1>[F:26][C:8]1([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 588007N-FluorobenzenesulfonimideHCID 2733832Lithium HexamethyldisilazideHCID 10488810Ethyl 1,4-dioxaspiro(4.5)decane-8-carboxylate

Product 1

HCID 67960160Ethyl 8-fluoro-1,4-dioxaspiro[4.5]decane-8-carboxylateYield 102.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate (15 g, 70.0 mmol, 1 equiv) in THF (200 mL) at 0° C. (ice water bath), was added LiHMDS (98 mL of a 1 M solution in THF, 98 mmol, 1.4 equiv) in 4 portions over ˜2 min. After stirring 1 h, N-fluoro-di(benzenesulfonyl)-amine (26.5 g, 84 mmol, 1.2 equiv) was added. The reaction was stirred 20 min then poured into a saturated aqueous solution of NaHCO3. The aqueous solution was extracted with ether (×3). The combined ether layers were dried (MgSO4) and concentrated in vacuo. Crude residue was stirred with hexane (˜600 mL) and filtered. The filtrate was concentrated in vacuo to give 16.68 g of the crude product as a yellow oil. ˜4:1 product:sm. Taken on as is to the ester reduction. 1H NMR (400 MHz, CDCl3) δ ppm 4.25 (q, J=7.11 Hz, 2H), 3.94-4.00 (m, 4H), 2.02-2.26 (m, 4H), 1.92 (td, J=13.30, 4.77 Hz, 2H), 1.66-1.77 (m, 2H), 1.31 (t, J=7.03 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ ppm −168.50 (br. s., 1F).

Workup

  1. stirringThe reaction was stirred 20 min
  2. extractionThe aqueous solution was extracted with ether (×3)
  3. dry with materialThe combined ether layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. stirringCrude residue was stirred with hexane (˜600 mL)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-ca878a4416d147d587b3412b370cf8f8
Source dataset
uspto-grants-2014_09
Patent number
US08835411B2

Reaction notes

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