Ethyl Acetate → HCID 58631154, compound

HRID 525607Notes

Reaction equation

HRID 525607 reaction equation
C(OCC)(=O)C.[C:7]([C:9]1[CH:14]=[CH:13][C:12]([C@H:15]2[O:19][C:18]([CH3:21])([CH3:20])[N:17]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@@H:16]2[CH2:29][F:30])=[CH:11][CH:10]=1)#[CH:8].Cl/[C:32](=[N:38]/[OH:39])/[C:33]([O:35][CH2:36][CH3:37])=[O:34].C(=O)([O-])O.[Na+]>CN(C)C=O>[C:25]([O:24][C:22]([N:17]1[C@H:16]([CH2:29][F:30])[C@@H:15]([C:12]2[CH:11]=[CH:10][C:9]([C:7]3[O:39][N:38]=[C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH:8]=3)=[CH:14][CH:13]=2)[O:19][C:18]1([CH3:21])[CH3:20])=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 6399471Ethyl 2-chloro-2-(hydroxyimino)acetateHCID 58631078HCID 58631078, compound

Product 1

HCID 58631154HCID 58631154, compoundYield 31.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ethyl acetate (20 ml) solution of (4S,5R)-tert-butyl 5-(4-ethynylphenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate (1.35 g, 4.0 mmol) is added a dimethylformamide solution of (E)-ethyl 2-chloro-2-(hydroxyimino)-acetate (12.5 ml, 1.5 g, 2.5 equiv). Sodium hydrogen carbonate (3.5 g) is added to the solution and it is allowed to stir overnight at room temperature. The mixture is filtered and diluted with ethyl acetate (100 ml). After washing with water (4×25 ml) the organic phase is concentrated to give the crude product, which is purified on silica gel using a gradient of ethyl acetate in hexanes (0% to 20% ethyl acetate) to give the title compound (567 mg): 1H NMR (400 MHz, CDCl3) 1.43-1.56 (m, 14 H) 1.62 (s, 3 H) 1.74 (br. s., 3 H) 4.50 (q, J=7.24 Hz, 3 H) 5.20 (d, J=7.33 Hz, 1 H) 6.96 (s, 1 H) 7.60 (d, J=8.34 Hz, 2 H) 7.86 (d, J=8.59 Hz, 2 H), m/z (Cl) 449 ([M+H]+.

Workup

  1. filtrationThe mixture is filtered
  2. additiondiluted with ethyl acetate (100 ml)
  3. washAfter washing with water (4×25 ml) the organic phase
  4. concentrationis concentrated
  5. customto give the crude product, which
  6. customis purified on silica gel using a gradient of ethyl acetate in hexanes (0% to 20% ethyl acetate)

Sources & evidence

ORD record
ord-3e99a78dfd7f4fdb9f47275d02a10d8b
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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