Diethyl Ether → HCID 86730049, compound

HRID 516951Notes

Reaction equation

HRID 516951 reaction equation
FC(F)(F)S(O[C:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C@H:17]3[CH2:26][CH2:25][C@@:19]4([NH:23][C:22](=[O:24])[O:21][CH2:20]4)[CH2:18]3)[CH:13]=2)[CH:8]=1)(=O)=O.CN1C(=O)CCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:46]([Mg]Br)[CH2:47][CH2:48][CH2:49][CH2:50][CH3:51].CCOCC>C1COCC1>[CH2:46]([C:7]1[CH2:16][CH2:15][C:14]2[CH:13]=[C:12]([C@H:17]3[CH2:26][CH2:25][C@@:19]4([NH:23][C:22](=[O:24])[O:21][CH2:20]4)[CH2:18]3)[CH:11]=[CH:10][C:9]=2[CH:8]=1)[CH2:47][CH2:48][CH2:49][CH2:50][CH3:51]

Participants

7

Reactant 5

HCID 3283Diethyl EtherHCID 13387N-methyl-2-pyrrolidoneHCID 2733832Lithium HexamethyldisilazideHCID 86730039HCID 86730039, compoundHCID 178444609HCID 178444609, compound

Product 1

HCID 86730049HCID 86730049, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 6-((5R,7S)-2-oxo-3-oxa-1-azaspiro[4.4]nonan-7-yl)-3,4-dihydronaphthalen-2-yl trifluoromethanesulfonate (Int. 6, 1 g, 2.396 mmol) and NMP (2.306 mL, 23.96 mmol) in THF (20 mL) at −40° C. was added a solution of lithium bis(trimethylsilyl)amide in THF (2.396 mL, 2.396 mmol). The reaction mixture was stirred for 15 minutes, and then ferric acetylacetonate (0.042 g, 0.120 mmol) and hexylmagnesium bromide in ether (2.396 mL, 4.79 mmol) were added. The reaction mixture was stirred for 30 minutes and quenched with water. The reaction mixture was diluted with ethyl acetate and washed with 1M HCl. The organic layer was dried with MgSO4, filtered and concentrated. The crude material was purified on a silica gel cartridge (40 g) using an EtOAc/hexane gradient (0-100% EtOAc over 12 CV) to afford 662 mg of (5R,7S)-7-(6-hexyl-7,8-dihydronaphthalen-2-yl)-3-oxa-1-azaspiro[4.4]nonan-2-one as a white solid. HPLC retention time=1.28 min (Condition G); LC/MS M+1=354: 1H NMR (400 MHz, chloroform-d) δ 7.03-6.88 (m, 3H), 6.21 (s, 1H), 5.16 (br. s., 1H), 4.44-4.15 (m, 2H), 3.13-2.96 (m, 1H), 2.80 (t, J=8.0 Hz, 2H), 2.47-2.08 (m, 6H), 2.05-1.93 (m, 2H), 1.90-1.73 (m, 1H), 1.68-1.43 (m, 4H), 1.41-1.22 (m, 5H), 1.01-0.83 (m, 3H).

Workup

  1. stirringThe reaction mixture was stirred for 30 minutes
  2. customquenched with water
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwashed with 1M HCl
  5. dry with materialThe organic layer was dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified on a silica gel cartridge (40 g)

Sources & evidence

ORD record
ord-44b75aa5600d49b7b864bb8adfcbe39b
Source dataset
uspto-grants-2015_08
Patent number
US09115054B2

Reaction notes

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