Dimethyl Sulfoxide → ethyl (7R,8S)-8-((S)-3-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl)-1,4-dioxa-spiro[4.5]decane-7-carboxylate

HRID 1866112Notes

Reaction equation

HRID 1866112 reaction equation
[SH3+].[I-].C(O[C@:11]([N:35]=[C:36]=[O:37])([C:17](=[O:34])[NH:18][C@H:19]1[CH2:28][CH2:27][C:22]2([O:26][CH2:25][CH2:24][O:23]2)[CH2:21][C@H:20]1[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:12][CH2:13][S+](C)C)C1C=CC=CC=1.[C:38](=[O:41])([O-])[O-].[Cs+].[Cs+].CS(C)=O>[Cl-].[Na+].O.C(OCC)(=O)C>[CH2:38]([O:41][C:36]([NH:35][C@H:11]1[CH2:12][CH2:13][N:18]([C@H:19]2[CH2:28][CH2:27][C:22]3([O:23][CH2:24][CH2:25][O:26]3)[CH2:21][C@H:20]2[C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:17]1=[O:34])=[O:37])[C:19]1[CH:28]=[CH:27][CH:22]=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10796Cesium carbonateHCID 3015009SulfoniumHCID 86618143[(S)-3-benzyloxy-carbonylamino-3-((7R,8S)-7-ethoxycarbonyl-1,4-dioxa-spiro[4.5]dec-8-ylcarbamoyl)-propyl]-dimethylsulfonium iodide

Product 1

HCID 57978126ethyl (7R,8S)-8-((S)-3-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl)-1,4-dioxa-spiro[4.5]decane-7-carboxylate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Example 1, 2nd Alternative Preparation, Step 2: Sulfonium salt 3 (619.4 g), and cesium carbonate (416.8 g) and anhydrous dimethyl sulfoxide (6.2 L) were combined in a reactor equipped with a scrubber to neutralize volatile sulfides. Vigorous agitation was maintained until complete conversion was obtained (HPLC). Ethyl acetate (12.4 L) was added, followed by 20% brine (3 L). The organic phase was separated, washed twice with brine (2×3 L) and evaporated to obtain a solution of ethyl (7R,8S)-8-((S)-3-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl)-1,4-dioxa-spiro[4.5]decane-7-carboxylate 4 in ethyl acetate (˜0.8 L). Acetone (2.55 L) was added, followed by aqueous 0.5 M hydrochloric acid solution (2.3 L). With good mixing, the solution was heated to 50 to 60° C. until conversion of 4 to ethyl (1R,2S)-2-((S)-3-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl)-5-oxo-cyclohexanecarboxylate 5 was complete (HPLC). The mixture was concentrated under reduced pressure while below 40° C., cooled to ˜30° C., and water (4.1 L) was added. The resulting slurry was cooled to 5 to 10° C. and agitated for ˜1 hour. The product was filtered and the cake was washed with water (2×2.5 L). Upon deliquoring, the cake was dried to a constant weight below 40° C. in a vacuum oven. Cyclohexanone 5 (272 g, 70% yield) was obtained (HPLC purity 98.7%).

Workup

  1. customExample 1, 2nd Alternative Preparation, Step 2
  2. customequipped with a scrubber
  3. temperatureVigorous agitation was maintained until complete conversion
  4. customwas obtained (HPLC)
  5. customThe organic phase was separated
  6. washwashed twice with brine (2×3 L)
  7. customevaporated

Sources & evidence

ORD record
ord-cc99eef353b546ec8afcb8722f46be61
Source dataset
uspto-grants-2009_12
Patent number
US07629351B2

Reaction notes

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