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

HRID 2242327Notes

Reaction equation

HRID 2242327 reaction equation
[SH3+].[I-].[CH2:3]([O:10][C:11]([NH:13][C@H:14]([C:20](=[O:37])[NH:21][C@H:22]1[CH2:31][CH2:30][C:25]2([O:29][CH2:28][CH2:27][O:26]2)[CH2:24][C@H:23]1[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:15][CH2:16][S+](C)C)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(C)=O>[Cl-].[Na+].O.C(OCC)(=O)C>[CH2:3]([O:10][C:11]([NH:13][C@H:14]1[CH2:15][CH2:16][N:21]([C@H:22]2[CH2:31][CH2:30][C:25]3([O:29][CH2:28][CH2:27][O:26]3)[CH2:24][C@H:23]2[C:32]([O:34][CH2:35][CH3:36])=[O:33])[C:20]1=[O:37])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10796Cesium carbonateHCID 3015009SulfoniumHCID 86618126HCID 86618126, compound

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, 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, 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-bb011b88d716467b971bec4467397161
Source dataset
uspto-grants-2010_03
Patent number
US07671062B2

Reaction notes

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