Water → HCID 76611649, compound

HRID 639871Notes

Reaction equation

HRID 639871 reaction equation
C[O:2][C:3]([C:5]1([CH:16]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[NH:11][C:10](=[O:12])[CH:9]([CH2:13][CH2:14][Cl:15])[C:6]21[O:8][CH2:7]2)=O.C(O[CH2:35][CH3:36])(=O)C.[OH2:37]>C[Si](C)(C)CCO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:25][Si:24]([CH3:27])([CH3:26])[CH2:35][CH2:36][O:37][C:3]([C:5]1([CH:16]([O:23][Si:24]([C:27]([CH3:28])([CH3:30])[CH3:29])([CH3:25])[CH3:26])[CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]2)[NH:11][C:10](=[O:12])[CH:9]([CH2:13][CH2:14][Cl:15])[C:6]21[O:8][CH2:7]2)=[O:2]

Participants

6

Reactant 3

HCID 962WaterHCID 8857Ethyl AcetateHCID 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 ester

Product 1

HCID 76611649HCID 76611649, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 180132-(Trimethylsilyl)ethanolSolvent

Conditions

Temperature
23 °C

Procedure

Titanium (IV) isopropoxide (0.30 ml, 0.42 g, 1.5 mmol, 11.5 equiv) was added to a stirred solution of 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 (60 mg, 0.13 mmol, 1.0 equiv) in 2-trimethylsilanyl-ethanol (1.5 ml), and the resultant solution was heated at 100° C. for 17 h. The reaction mixture was allowed to cool to 23° C. and ethyl acetate (30 ml) and water (20 ml) was added. The resultant solution was stirred for 10 min and filtered through Celite. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (15 ml×2). The combined organic layers were dried over sodium sulfate and the solids were filtered. The filtrate was concentrated. The residue was purified by flash column chromatography (10% ethyl acetate-hexanes initially, grading to 20% ethyl acetate-hexanes) to afford 4-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-7-(2-chloro-ethyl)-6-oxo-1-oxa-5-aza-spiro[2.4]heptane-4-carboxylic acid 2-trimethylsilanyl-ethyl ester (61 mg, 74%) as a colorless oil.

Workup

  1. filtrationfiltered through Celite
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (15 ml×2)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationthe solids were filtered
  6. concentrationThe filtrate was concentrated
  7. customThe residue was purified by flash column chromatography (10% ethyl acetate-hexanes initially

Sources & evidence

ORD record
ord-37f0de1e4846407e930a79a0563f07ff
Source dataset
uspto-grants-2010_04
Patent number
US07691896B2

Reaction notes

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