Sodium hydride → Tert-butyl 2-[cis-3-(5-methyl-2-p-tolyloxazol-4-ylmethoxy)cyclohexylmethoxy]-2-methylpropionate

HRID 854644Notes

Reaction equation

HRID 854644 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([CH2:8][O:9][C:10]([CH3:19])([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:3]1.[H-].[Na+].[CH3:22][C:23]1[O:27][C:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)=[N:25][C:24]=1[CH2:35]I.[NH4+].[Cl-]>CN(C)C=O.C(OC)(C)(C)C>[CH3:22][C:23]1[O:27][C:26]([C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)=[N:25][C:24]=1[CH2:35][O:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][C@H:4]([CH2:8][O:9][C:10]([CH3:19])([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:3]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 219803112-(4-Methylphenyl)-4-iodomethyl-5-methyloxazoleHCID 67214679Tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)-2-methylpropionate

Product 1

HCID 69242284Tert-butyl 2-[cis-3-(5-methyl-2-p-tolyloxazol-4-ylmethoxy)cyclohexylmethoxy]-2-methylpropionateYield 59.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

200 mg of tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)-2-methyl-propionate are dissolved in 5 ml of dimethylformamide, and 20 mg of NaH (95%) are added. After 60 min of stirring at room temperature, 460 mg of 5-methyl-2-p-tolyloxazol-4-ylmethyl iodide in 1.5 ml of dimethylformamide are added at 0° C. The mixture is stirred at room temperature for 2 h. 10 ml of methyl tert-butyl ether and 10 ml of saturated NH4Cl solution are then added. The phases are separated, the aqueous phase is extracted once with methyl tert-butyl ether and the organic phases are dried over MgSO4 and concentrated. The residue is chromatographed on silica gel (heptane/ethyl acetate 5/1->1/1). 200 mg of the crude tert-butyl 2-[cis-3-(5-methyl-2-p-tolyloxazol-4-ylmethoxy)cyclohexylmethoxy]-2-methylpropionate are obtained as a yellow oil. C27H39NO5 (457), LCMS (ESI): 458 (MH+).

Workup

  1. stirringThe mixture is stirred at room temperature for 2 h
  2. customThe phases are separated
  3. extractionthe aqueous phase is extracted once with methyl tert-butyl ether
  4. dry with materialthe organic phases are dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue is chromatographed on silica gel (heptane/ethyl acetate 5/1->1/1)

Sources & evidence

ORD record
ord-77ec3203adfa4593a25b625535bbe3b4
Source dataset
uspto-grants-2007_08
Patent number
US07259177B2

Reaction notes

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