1,1'-Carbonyldiimidazole → [1(S)-(Methoxy-methyl-carbamoyl)-2,2-dimethylpropyl]-carbamic Acid-tert-butyl Ester

HRID 2084530Notes

Reaction equation

HRID 2084530 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:30][O:31][NH:32][CH3:33]>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:10](=[O:12])[N:32]([O:31][CH3:30])[CH3:33])[C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2734668(S)-2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoic acid

Product 1

HCID 53879830[1(S)-(Methoxy-methyl-carbamoyl)-2,2-dimethylpropyl]-carbamic Acid-tert-butyl EsterYield 74.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2(S)-tert-butoxycarbonylamino-3,3-dimethyl-butyric acid (30 g, 0.13 mol) in dichloromethane (400 mL) was added portionwise 1,1′-carbonyidiimidazole (63.3 g, 0.39 mol). After addition was complete the reaction was allowed to stir for 15 minutes before N-methoxy-N-methylamine hydrochloride (38 g, 0.39 mol) was added and the reaction allowed to stir for 16 hours. The solvents were removed in vacuo and the residue partitioned between ethyl acetate (250 mL) and 1M HCl (150 mL). The organic phase was washed with 1M HCl solution (2×100 mL), saturated sodium bicarbonate solution (2×100 mL) and brine (100 mL). The organic phase was dried over MgSO4, filtered and the solvents removed in vacuo to give a crude yellow oil. Purification by column chromatography (SiO2, 30% ethyl acetate in hexanes) afforded the title product as a pale yellow oil (26.5 g, 74%).

Workup

  1. additionAfter addition
  2. additionwas added
  3. customThe solvents were removed in vacuo
  4. customthe residue partitioned between ethyl acetate (250 mL) and 1M HCl (150 mL)
  5. washThe organic phase was washed with 1M HCl solution (2×100 mL), saturated sodium bicarbonate solution (2×100 mL) and brine (100 mL)
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. customthe solvents removed in vacuo
  9. customto give a crude yellow oil
  10. customPurification by column chromatography (SiO2, 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5acaaec56db14aba8b1211e307fccc91
Source dataset
uspto-grants-2004_04
Patent number
US06716878B1

Reaction notes

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