Ammonium Chloride → Tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)pentanoate

HRID 854642Notes

Reaction equation

HRID 854642 reaction equation
COC[O:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][C@H:7]([CH2:11][O:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:6]1.C(=O)=O.[CH3:24][C:25]([CH3:27])=O.C([N-]C(C)C)(C)C.[Li+].C(I)CC.[Cl-].[NH4+]>O1CCCC1.CCCCCC.O1CCCC1>[OH:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][C@H:7]([CH2:11][O:12][CH:13]([CH2:24][CH2:25][CH3:27])[C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:6]1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 336431-IodopropaneHCID 2724682Lithium diisopropylamideHCID 18522661Acetone cardiceHCID 69244811Tert-butyl (cis-3-methoxymethoxycyclohexylmethoxy)acetate

Product 1

HCID 69243692Tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)pentanoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21883165Tetrahydrofuran hexaneSolvent

Conditions

Temperature
-78 °C

Procedure

200 mg of tert-butyl (cis-3-methoxymethoxycyclohexylmethoxy)acetate are dissolved in 5 ml of abs. tetrahydrofuran and cooled to −78° C. (dry ice/acetone bath). 0.7 ml of a 2M lithium diisopropylamide solution in tetrahydrofuran/hexane is then added dropwise. The solution is initially stirred at −78° C. and then warmed to 0° C. (ice bath) and stirred at this temperature for 20 min. 600 mg of propyl iodide in 2 ml of tetrahydrofuran are then added, and the solution is stirred at 0° C. for a further 2.5 h. 15 ml of a saturated ammonium chloride solution are added, and the phases are separated. The aqueous phase is extracted with methyl tert-butyl ether. The combined organic phases are dried over MgSO4 and concentrated (yield: 240 mg of crude product). The residue is taken up in 2 ml of tetrahydrofuran, 0.5 ml of conc. HCl is added and the mixture is stirred at room temperature for 18 h. The mixture is diluted with water and methyl tert-butyl ether, the phases are separated and the aqueous phase is extracted with methyl tert-butyl ether. The combined organic phases are washed with saturated NaCl solution, dried over MgSO4 and concentrated. This gives 130 mg of tert-butyl 2-(cis-3-hydroxycyclohexylmethoxy)-pentanoate as a yellow oil. NMR (CDCl3) diastereomer mixture: 3.55-3.67 (m, 2H), 3.41-3.48 (m, 1H), 3.07-3.18 (m, 1H), 1.91-2.13 (m, 2H), 1.11-1.82 (m, 14H), 1.48 (s, 9H).

Workup

  1. temperaturewarmed to 0° C. (ice bath)
  2. stirringstirred at this temperature for 20 min
  3. stirringthe solution is stirred at 0° C. for a further 2.5 h
  4. customthe phases are separated
  5. extractionThe aqueous phase is extracted with methyl tert-butyl ether
  6. dry with materialThe combined organic phases are dried over MgSO4
  7. concentrationconcentrated (yield: 240 mg of crude product)
  8. addition0.5 ml of conc. HCl is added
  9. stirringthe mixture is stirred at room temperature for 18 h
  10. additionThe mixture is diluted with water and methyl tert-butyl ether
  11. customthe phases are separated
  12. extractionthe aqueous phase is extracted with methyl tert-butyl ether
  13. washThe combined organic phases are washed with saturated NaCl solution
  14. dry with materialdried over MgSO4
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-5f41e0ee44964ad09dca1876b1e03f6d
Source dataset
uspto-grants-2007_08
Patent number
US07259177B2

Reaction notes

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