Sodium Iodide → (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3,5-dimethyl-benzylamide

HRID 2353615Notes

Reaction equation

HRID 2353615 reaction equation
[OH:1][C:2]1[C:23]([CH3:24])=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:17][C:16]([CH3:18])=[C:15]3[C:11]=2[CH2:12][C@H:13]2[C:19]([CH3:21])([CH3:20])[C@H:14]23)=[O:9])=[CH:4][C:3]=1[CH3:25].[Na+].[I-].[CH3:28][C:29]1([CH3:41])[O:34][CH2:33][CH:32]([CH2:35]OS(C)(=O)=O)[CH2:31][O:30]1>C(O)(C)C.[OH-].[Na+]>[CH3:28][C:29]1([CH3:41])[O:34][CH2:33][CH:32]([CH2:35][O:1][C:2]2[C:23]([CH3:24])=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]3[S:17][C:16]([CH3:18])=[C:15]4[C:11]=3[CH2:12][C@H:13]3[C:19]([CH3:21])([CH3:20])[C@H:14]34)=[O:9])=[CH:4][C:3]=2[CH3:25])[CH2:31][O:30]1

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 10998661(2,2-Dimethyl-1,3-dioxan-5-yl)methyl methanesulfonateHCID 68452739(1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-hydroxy-3,5-dimethyl-benzylamide

Product 1

HCID 68451511(1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3,5-dimethyl-benzylamide

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 14798Sodium HydroxideSolvent2×

Procedure

To a solution of (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-hydroxy-3,5-dimethyl-benzylamide (28.8 mg, 0.08 mmol, Example 5 step b) in isopropanol (3.5 mL) and 2 N aq. NaOH (0.6 mL) is added a catalytic amount of NaI followed by methanesulfonic acid 2,2-dimethyl-[1,3]dioxan-5-ylmethyl ester (90 mg, 0.40 mmol, B. Xu, G. Kirschenheuter, A. F. Greslin, X. Cheng, J. Sennelo, M. Cattaneo, M. L. Zighetti, A. Chen, S.-A, Kim, H. S. Kim, N. Bischofberger, G. Cook, K. A. Jacobson, J. Med. Chem. 45 (2002) 5694-5709). The reaction mixture is shaken at rt for 8 h, diluted with 1 N aq. NaOH, and extracted twice with DCM. The organic extracts are dried over MgSO4, filtered and evaporated. The residue is purified by prep. HPLC to give (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3,5-dimethyl-benzylamide (28 mg) as a colourless solid. LC-MS: tR=1.13 min, [M+1]+=484.34.

Workup

  1. extractionextracted twice with DCM
  2. dry with materialThe organic extracts are dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue is purified by prep

Sources & evidence

ORD record
ord-97a9b190da754819a52c89d694f0e525
Source dataset
uspto-grants-2010_07
Patent number
US07750040B2

Reaction notes

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