Triethylamine → [3,3-dimethyl-1(S)-(4-methyl-2,6,7-trioxabicyclo[2.2.2]oct-1-yl)butyl]carbamic acid benzyl ester

HRID 907616Notes

Reaction equation

HRID 907616 reaction equation
[CH3:1][C:2]1([CH2:6][O:7][C:8](=[O:26])[C@@H:9]([NH:15][C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:5][O:4][CH2:3]1.C(N(CC)CC)C>C(Cl)Cl.B(F)(F)F.CCOCC>[CH2:19]([O:18][C:16](=[O:17])[NH:15][C@H:9]([C:8]12[O:4][CH2:5][C:2]([CH3:1])([CH2:3][O:26]1)[CH2:6][O:7]2)[CH2:10][C:11]([CH3:12])([CH3:14])[CH3:13])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 673918222(S)-benzyloxycarbonylamino-4,4-dimethylpentanoic acid 3-methyloxetan-3-ylmethyl ester

Product 1

HCID 67391458[3,3-dimethyl-1(S)-(4-methyl-2,6,7-trioxabicyclo[2.2.2]oct-1-yl)butyl]carbamic acid benzyl esterYield 72.3%

Reagents, catalysts & solvents 2

HCID 8000Boron trifluoride etherateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2(S)-benzyloxycarbonylamino-4,4-dimethylpentanoic acid 3-methyl-oxetan-3-ylmethyl ester (21.5 g, 59 mmol) in dry DCM (50 ml) was added BF3.Et2O (0.4 ml, 3.2 mmol). After 5 h, triethylamine (0.9 ml, 6.4 mmol) was added and stirring was continued for 30 min at room temperature. The solvent was evaporated using a rotavap and the resulting oil was redissolved in ethyl acetate and was washed with 50 ml of 3% NH4Cl solution followed by brine. The ethyl acetate layer was dried over MgSO4, the solvent was evaporated and the residue was purified with column chromatography using silica gel and 20:80 EtOAc:Hexane as eluent to give [3,3-dimethyl-1(S)-(4-methyl-2,6,7-trioxabicyclo[2.2.2]oct-1-yl)butyl]carbamic acid benzyl ester (15.5 g).

Workup

  1. waitwas continued for 30 min at room temperature
  2. customThe solvent was evaporated
  3. dissolutionthe resulting oil was redissolved in ethyl acetate
  4. washwas washed with 50 ml of 3% NH4Cl solution
  5. dry with materialThe ethyl acetate layer was dried over MgSO4
  6. customthe solvent was evaporated
  7. customthe residue was purified with column chromatography

Sources & evidence

ORD record
ord-2f239e58a85a4ff5b338967acd59a687
Source dataset
uspto-grants-2011_09
Patent number
US08013186B2

Reaction notes

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