Sodium Methoxide → HCID 178495641, compound

HRID 1257696Notes

Reaction equation

HRID 1257696 reaction equation
[CH3:1][O-].[Na+].[C:4]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([CH2:18][O:19]S(C)(=O)=O)[CH2:14][CH2:13]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>CO.C1COCC1>[C:4]([O:8][C:9](=[O:10])[NH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([CH2:18][O:19][CH3:1])[CH2:14][CH2:13]1)([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 178453973HCID 178453973, compound

Product 1

HCID 178495641HCID 178495641, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of sodium methoxide in methanol (6.0 mL of a 25% solution, ˜27.0 mmol) was added to a solution of trans methanesulfonic acid 4-tert-butoxycarbonylamino-cyclohexylmethyl ester (1.50 g, 4.88 mmol) in THF (15 mL) and methanol (15 mL). The mixture was heated at reflux for 6.75 hours. The cold mixture was concentrated under vacuum to remove most of the solvent then diluted with water (10 mL). The mixture was then cautiously neutralised with 1M hydrochloric acid then extracted with DCM (3×20 mL). The combined organic phase was dried over magnesium sulphate and concentrated under vacuum. The residue was purified by chromatography on silica gel (eluting with 9:1 cyclohexane:ethyl acetate) to afford 1.07 g (90%) of trans (4-methoxymethyl-cyclohexyl)-carbamic acid tert-butyl ester as a white solid. 1H NMR (400 MHz, CDCl3): δ 4.36 (br s, 1H), 3.37 (br s, 1H), 3.32 (s, 3H), 3.18 (d, 2H), 2.07-1.97 (m, 2H), 1.84-1.75 (m, 2H), 1.56-1.45 (m, 1H), 1.44 (s, 9H), 1.16-0.96 (m, 4H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 6.75 hours
  3. concentrationThe cold mixture was concentrated under vacuum
  4. customto remove most of the solvent
  5. additionthen diluted with water (10 mL)
  6. extractionthen extracted with DCM (3×20 mL)
  7. dry with materialThe combined organic phase was dried over magnesium sulphate
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by chromatography on silica gel (eluting with 9:1 cyclohexane:ethyl acetate)

Sources & evidence

ORD record
ord-c27693cdcf2343dea3dc2d78aaadd7bd
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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