Sodium hydride → (E)-butoxyimino-[(2S)-2-[[(3S)-3-(4-chlorophenyl)-6-methyl-1,3-dihydrofuro[3,4-c]pyridin-7-yl]oxycarbonyloxymethyl]pyrrolidin-1-yl]-oxidoazanium

HRID 388217Notes

Reaction equation

HRID 388217 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C:12]3[CH:13]=[N:14][C:15]([CH3:18])=[C:16]([OH:17])[C:11]=3[CH2:10][O:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[C:21](=O)([O:37]C(Cl)C)[O:22][CH2:23][C@@H:24]1[CH2:28][CH2:27][CH2:26][N:25]1/[N+:29](/[O-:36])=[N:30]/[O:31][CH2:32][CH2:33][CH2:34][CH3:35]>CN(C=O)C>[C:21](=[O:37])([O:17][C:16]1[C:11]2[CH2:10][O:9][C@@H:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[C:12]=2[CH:13]=[N:14][C:15]=1[CH3:18])[O:22][CH2:23][C@@H:24]1[CH2:28][CH2:27][CH2:26][N:25]1/[N+:29](/[O-:36])=[N:30]\[O:31][CH2:32][CH2:33][CH2:34][CH3:35]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11680500Cicletanine, (S)-HCID 88851464(Z)-butoxyimino-[(2S)-2-(1-chloroethoxycarbonyloxymethyl)pyrrolidin-1-yl]-oxidoazanium

Product 1

HCID 51347910(E)-butoxyimino-[(2S)-2-[[(3S)-3-(4-chlorophenyl)-6-methyl-1,3-dihydrofuro[3,4-c]pyridin-7-yl]oxycarbonyloxymethyl]pyrrolidin-1-yl]-oxidoazanium

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S)-3-(4-chlorophenyl)-6-methyl-1,3-dihydrofuro[3,4-c]pyridine-7-ol (900 mg, 3.44 mmol) in DMF (10 mL) at 0° C. was added sodium hydride (206 mg, 5.16 mmol) and, in 10 minutes, followed by addition of {(2S)-1-[(Z)-butoxy-NNO-azoxy]pyrrolidin-2-yl}methyl 1-chloroethyl carbonate (1.3 g, 4.02 mmol). After stirring at rt for 3 h, the mixture was partitioned between Et2O (50 mL) and water (50 mL). The organic layer was washed with brine (3×50 mL), dried over MgSO4, and concentrated. The residue was purified by flash chromatography (Biotage 25+M) using 30-50% EtOAc/hexane gradient, affording the title compound: 1H NMR (500 MHz, CDCl3) δ 8.08 (s, 1H), 7.37-7.27 (m, 4H), 6.21 (s, 1H), 5.29-5.13 (m, 2H), 4.49 (m, 1H), 4.40 (m, 1H), 4.35 (m, 1H), 4.20 (m, 2H), 3.65 (m, 1H), 3.57 (m, 1H), 2.52 (s, 3H), 2.20 (m, 1H), 2.05 (m, 2H), 1.90 (m, 1H), 1.75 (m, 2H), 1.42 (m, 2H), 0.94 (m, 3H).

Workup

  1. customthe mixture was partitioned between Et2O (50 mL) and water (50 mL)
  2. washThe organic layer was washed with brine (3×50 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (Biotage 25+M)

Sources & evidence

ORD record
ord-6dab702b1b604d12b2b2450ac90b66be
Source dataset
uspto-grants-2013_02
Patent number
US08377911B2

Reaction notes

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