Methyl trifluoromethyl ketone → 4-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-7-(2-chloro-ethyl)-6-oxo-1-oxa-5-aza-spiro[2.4]heptane-4-carboxylic acid methyl ester

HRID 639870Notes

Reaction equation

HRID 639870 reaction equation
[Na].[Na].C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=[O:8].[CH3:23][O:24][C:25]([C:27]1([CH:37]([O:44][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[C:31](=[CH2:32])[CH:30]([CH2:33][CH2:34][Cl:35])[C:29](=[O:36])[NH:28]1)=[O:26].FC(F)(F)C(=O)C.C(=O)(O)[O-].[Na+].OOS([O-])=O.[K+]>C(#N)C.O>[CH3:23][O:24][C:25]([C:27]1([CH:37]([O:44][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH:38]2[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]2)[NH:28][C:29](=[O:36])[CH:30]([CH2:33][CH2:34][Cl:35])[C:31]21[O:8][CH2:32]2)=[O:26]

Participants

8

Reactant 5

HCID 9871Methyl trifluoromethyl ketoneHCID 516892Sodium BicarbonateHCID 9949814Ethylenediaminetetraacetic acid disodiumHCID 23707502Potassium hydroxy sulfiteHCID 685773462-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-4-(2-chloro-ethyl)-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester

Product 1

HCID 766116584-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-7-(2-chloro-ethyl)-6-oxo-1-oxa-5-aza-spiro[2.4]heptane-4-carboxylic acid methyl esterYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

An aqueous ethylenediaminetetraacetic acid disodium solution (1.04 ml, 4×10−4 M) was added to a stirred solution of 2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-4-(2-chloro-ethyl)-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester (71 mg, 0.16 mmol, 1.0 equiv) in acetonitrile (2.6 ml) and the reaction mixture was cooled to 0° C. Trifluoroacetone (0.6 ml) was added via a precooled syringe. A mixture of sodium bicarbonate (0.313 g, 3.72 mmol, 23.25 equiv) and Oxone (0.738 g, 1.2 mmol, 7.5 equiv) was added. The reaction mixture was stirred for 4 h at 0° C. Water (20 ml) was added and the resultant mixture was extracted with dichloromethane (100 ml). The organic layer was separated, dried over sodium sulfate and the solids were filtered. The filtrate was concentrated. Purification of the residue by flash column chromatography (15% ethyl acetate-hexanes initially, grading to 20% ethyl acetate-hexanes) provided 4-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-7-(2-chloro-ethyl)-6-oxo-1-oxa-5-aza-spiro[2.4]heptane-4-carboxylic acid methyl ester (53 mg, 72%).

Workup

  1. additionwas added
  2. extractionthe resultant mixture was extracted with dichloromethane (100 ml)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationthe solids were filtered
  6. concentrationThe filtrate was concentrated
  7. customPurification of the residue by flash column chromatography (15% ethyl acetate-hexanes initially

Sources & evidence

ORD record
ord-90270c2d430c49c7a55f0f9692434187
Source dataset
uspto-grants-2010_04
Patent number
US07691896B2

Reaction notes

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