Lithium hydroxide, monohydrate → 1-(((tert-Butoxycarbonyl)amino)methyl)spiro[2.5]octane-1-carboxylic acid

HRID 1297222Notes

Reaction equation

HRID 1297222 reaction equation
C[O:2][C:3]([C:5]1([CH2:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:7]2([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:6]1)=[O:4].O[Li].O>O>[C:18]([O:17][C:15]([NH:14][CH2:13][C:5]1([C:3]([OH:4])=[O:2])[C:7]2([CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:6]1)=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 112318021-(Tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid methyl ester

Product 1

HCID 118184231-(((tert-Butoxycarbonyl)amino)methyl)spiro[2.5]octane-1-carboxylic acidYield 63%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of crude 1-(tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid methyl ester (35.0 g, ˜96.2 mmol) was added LiOH—H2O (12.3 g, 294 mmol) followed by the addition of water (75 mL). The mixture was heated to reflux. After 48 hours, an additional portion of LiOH—H2O (6.15 g, 146 mmol) was added and refluxed for an additional 24 hours. The solvent was removed under reduced vacuum. The residue was partitioned between water and ether. The aqueous layer was acidified to pH 2-3 with aqueous HCl with ice bath cooling with a layer of CH2Cl2 present. The layers were separated and the aqueous layer was extracted with CH2Cl2 (3 times). The combined organic layers were dried over sodium sulfate, filtered and evaporated to give 17.0 g (63%, 2 steps) of 1-(tert-butoxycarbonylamino-methyl)-spiro[2.5]octane-1-carboxylic acid an off-white solid.

Workup

  1. temperatureThe mixture was heated to reflux
  2. temperaturerefluxed for an additional 24 hours
  3. customThe solvent was removed under reduced vacuum
  4. customThe residue was partitioned between water and ether
  5. customThe aqueous layer was acidified to pH 2-3 with aqueous HCl with ice bath
  6. temperaturecooling with a layer of CH2Cl2 present
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with CH2Cl2 (3 times)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-a3b252201d4045f6b422cc6160d0601e
Source dataset
uspto-grants-2007_07
Patent number
US07250433B2

Reaction notes

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