Ammonia → (1S,3R)-benzyl 3-acetamido-2,2-dimethylcyclobutanecarboxylate

HRID 2179727Notes

Reaction equation

HRID 2179727 reaction equation
C([C@@H:4]1[CH2:7][C@H:6]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[C:5]1([CH3:19])[CH3:18])(=O)C.[N-]=[N+]=[N-].[Na+].CS(O)(=O)=O.[NH3:29].[CH2:30]([CH2:33]OC)[O:31]C>>[C:30]([NH:29][C@@H:4]1[CH2:7][C@H:6]([C:8]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:9])[C:5]1([CH3:18])[CH3:19])(=[O:31])[CH3:33]

Participants

6

Reactant 5

HCID 222AmmoniaHCID 6395Methanesulfonic AcidHCID 80711,2-DimethoxyethaneHCID 33557Sodium AzideHCID 58111012(1S,3R)-benzyl 3-acetyl-2,2-dimethylcyclobutanecarboxylate

Product 1

HCID 86650107(1S,3R)-benzyl 3-acetamido-2,2-dimethylcyclobutanecarboxylateYield 82.2%

Procedure

A stirred solution of (1S,3R)-benzyl 3-acetyl-2,2-dimethylcyclobutanecarboxylate (1.5 g, 5.76 mmol) in monoglyme (18.75 ml) at −45° C., NaN3 (1.12 g, 17.30 mmol), MeSO3H (10.5 ml), were added drop wise slowly and the reaction was allowed to stir at room temperature for about 48 hours. After completion of the reaction (monitored by TLC), the reaction mixture was neutralized with aqueous ammonia solution. Solvent was evaporated and diluted with DCM. Organic layer was washed with water, brine dried over Na2SO4. The solvent was evaporated under reduced pressure and the resulting crude purified by silica gel column (60/120 mesh, elution: 30% EtOAc in Hexane) to afford the title compound as off white solid. Wt: 1.3 g; Yield: 82.2%; 1H NMR (300 MHZ, CD3OD): δ 7.42-7.31 (m, 5H), 5.59 (d, 1H, J=5.7 Hz), 5.12 (s, 2H), 4.13 (q, 1H, J=9.3 Hz), 2.69-2.63 (m, 1H), 2.38-2.34 (m, 1H), 2.13-2.06 (m, 1H), 2.05 (s, 3H), 1.30 (s, 3H), 0.86 (s, 3H). Mass: [M+1]+ 276 (100%), [M+Na]+ 298 (66%); IR (KBr, cm−1): 3270, 2963, 2866, 1728, 1647, 1571, 1455, 1303, 1151, 1071, 1019, 961, 755, 742; M.R: 85.6° C.-97.5° C.

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. customSolvent was evaporated
  3. additiondiluted with DCM
  4. washOrganic layer was washed with water, brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was evaporated under reduced pressure
  7. customthe resulting crude purified by silica gel column (60/120 mesh, elution: 30% EtOAc in Hexane)

Sources & evidence

ORD record
ord-7784a036fad24a98a232ad1c7909d280
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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