Water → HCID 69515820, compound

HRID 1297224Notes

Reaction equation

HRID 1297224 reaction equation
C[O:2][C:3]([C:5]1([CH2:12][NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:7]2([CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:6]1)=[O:4].O[Li].O.O>CO>[C:17]([O:16][C:14]([NH:13][CH2:12][C:5]1([C:3]([OH:4])=[O:2])[C:7]2([CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:6]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 962Water2×HCID 168937Lithium hydroxide, monohydrateHCID 69515827HCID 69515827, compound

Product 1

HCID 69515820HCID 69515820, compoundYield 80.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 1-(tert-butoxycarbonylaminomethyl)-spiro[2.4]heptane-1-carboxylic acid methyl ester (16.5 g, 58.2 mmol) in methanol (100 mL) was added LiOH—H2O (4.9 g, 116 mmol) and water (15 mL). After 3 hours, additional methanol (50 mL) and water (15 mL) was added and reflux was continued for 6 hours total. The solvent was removed under reduced pressure. The residue was dissolved in water (200 mL) and washed with ether (200 mL). The aqueous solution was cooled in an ice bath and methylene chloride (200 mL) was added. With stirring, 4N HCl was added dropwise until pH=2-3. The layers were separated and the aqueous layer was extracted with methylene chloride (2×300 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. The residue was dissolved in hexane and evaporated to give 12.6 g (80%) of 1-(tert-butoxycarbonylaminomethyl)-spiro[2.4]heptane-1-carboxylic acid as a white foamy solid: 1H NMR (300 MHz, CDCl3) δ 1.08 (d, J=5.0 Hz, 1H), 1.44 (s, 9H), 1.45 (m, 2H), 1.55-1.8 (m, 6H), 1.92 (m, 1H), 3.35 (dd, J=6.0, 14.0 Hz, 1H), 3.44 (dd, J=6.0, 14.0 Hz, 1H), 5.28 (br t, 1H); MS (APCI) m/z=170 [M+H-100(Boc)]+.

Workup

  1. temperaturereflux
  2. waitwas continued for 6 hours
  3. customThe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in water (200 mL)
  5. washwashed with ether (200 mL)
  6. temperatureThe aqueous solution was cooled in an ice bath
  7. additionmethylene chloride (200 mL) was added
  8. addition4N HCl was added dropwise until pH=2-3
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted with methylene chloride (2×300 mL)
  11. dry with materialThe combined organic layers were dried over sodium sulfate
  12. filtrationfiltered
  13. customevaporated
  14. dissolutionThe residue was dissolved in hexane
  15. customevaporated

Sources & evidence

ORD record
ord-c7d9512647ae4a7a86ef8272ef04b0ee
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

Loading…