Ethyl Acetate → (S)-[2-(6-cyclopropoxy-2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-8-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester

HRID 397321Notes

Reaction equation

HRID 397321 reaction equation
C([Li])CCC.[CH:6]1([O:9][C:10]2[CH:18]=[CH:17][C:16]3[N:15]4[CH2:19][CH2:20][CH2:21][C:14]4=[C:13](I)[C:12]=3[CH:11]=2)[CH2:8][CH2:7]1.[C:23]([O:27][C:28]([N:30]1[C@@H:34]([CH3:35])[CH2:33]OS1(=O)=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].C(OCC)(=O)C>CCCCCC.O1CCCC1>[C:23]([O:27][C:28](=[O:29])[NH:30][C@@H:34]([CH3:33])[CH2:35][C:13]1[C:12]2[CH:11]=[C:10]([O:9][CH:6]3[CH2:8][CH2:7]3)[CH:18]=[CH:17][C:16]=2[N:15]2[CH2:19][CH2:20][CH2:21][C:14]=12)([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 109882941,2,3-Oxathiazolidine-3-carboxylic acid, 4-methyl-, 1,1-dimethylethyl ester, 2,2-dioxide, (4S)-HCID 230001116-cyclopropoxy-8-iodo-2,3-dihydro-1H-3a-aza-cyclopenta[a]indeneHCID 178418339Butyllithium

Product 1

HCID 69363623(S)-[2-(6-cyclopropoxy-2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-8-yl)-1-methyl-ethyl]-carbamic acid tert-butyl esterYield 58.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

37.4 mL of a 1.6 M solution of n-butyllithium in n-hexane was added at −78° C. dropwise during 10 min to a solution of 18.65 g 6-cyclopropoxy-8-iodo-2,3-dihydro-1H-3a-aza-cyclopenta[a]indene in 250 mL tetrahydrofuran. The mixture was stirred at −78° C. for 30 min. 15.55 g (S)-4-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester was added to the resulting suspension and the mixture stirred at −78° C. for 30 min and at 0° C. for 45 min. The reaction mixture was distributed between ice-cold 10% citric acid and ethyl acetate. The phases separated, the organic phase washed with water and brine, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with hexane: ethyl acetate=4: 1 to yield 11.91 g (S)-[2-(6-cyclopropoxy-2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-8-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester as beige crystals melting at 83-84° C.

Workup

  1. stirringthe mixture stirred at −78° C. for 30 min and at 0° C. for 45 min
  2. customThe phases separated
  3. washthe organic phase washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated
  6. customThe residue was purified by chromatography on silica gel with hexane

Sources & evidence

ORD record
ord-e3599478dc4c4607af92b32182a693d0
Source dataset
uspto-grants-2003_08
Patent number
US06610685B2

Reaction notes

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