Trifluoromethanesulfonic acid → (1S,2R,3R,5R,6S)-2-azido-3-benzyloxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-benzyl ester 6-ethyl ester

HRID 1872459Notes

Reaction equation

HRID 1872459 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:11]2[C@H:7]1[CH2:8][C@@H:9]([OH:25])[C@@:10]2([N:22]=[N+:23]=[N-:24])[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[O:5])[CH3:2].ClC(Cl)(Cl)C(=N)O[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.S(O)(C(F)(F)F)(=O)=O>C1CCCCC1.C(Cl)Cl.CCOCC>[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:11]2[C@H:7]1[CH2:8][C@@H:9]([O:25][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C@@:10]2([N:22]=[N+:23]=[N-:24])[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 62406Trifluoromethanesulfonic acidHCID 144968Benzyl 2,2,2-trichloroacetimidateHCID 11772339HCID 11772339, compound

Product 1

HCID 86755671(1S,2R,3R,5R,6S)-2-azido-3-benzyloxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-benzyl ester 6-ethyl esterYield 27%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8078CyclohexaneSolvent

Procedure

To a solution of (1S,2R,3R,5R,6S)-2-azido-3-hydroxy-bicyclo [3.1.0]hexane-2,6-dicarboxylic acid 2-benzyl ester 6-ethyl ester (VII) (305 mg, 0.88 mmol) and benzyl 2,2,2-trichloroacetimidate (0.2 mL, 1.06 mmol) in cyclohexane (2.4 mL) and DCM (1.2 mL) was added TfOH (0.05 mL), whereupon the solution became hot and stirring was continued at 23° C. for 5 h. The reaction mixture was poured on ice, diluted with ether, washed with sat. NaHCO3 -sol., brine and dried over MgSO4. The crude product was purified by silica gel column chromatography with hexane/EtOAc 4:1 to give (1S,2R,3R,5R,6S)-2-azido-3-benzyloxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid 2-benzyl ester 6-ethyl ester (XXIII-3) (102 mg, 27%) as a yellow oil. 1H-NMR (250 MHz, CDCl3) □1.25 (3H, t, J=7.1 Hz), 1.75 (1H, t, J=3.5 Hz), 2.06 (1H, m), 2.17-2.31 (3H, m), 3.60 (1H, bt, J=8 Hz), 4.12 (2H, q, j=7.1 Hz), 4.42 (1H, d, J=12 Hz), 4.57 (1H, d,J=12 Hz), 5.23 (1H, d,J=12 Hz), 5.34 (1H, d,J=12 Hz), 7.15-7.42 (10H, m); MS[ISP] 408 [(M+H-N2)+ ]; □D20 +2.03 ° (c=0.99, CHCl3).

Workup

  1. additionThe reaction mixture was poured on ice
  2. washwashed with sat. NaHCO3 -sol
  3. dry with material, brine and dried over MgSO4
  4. customThe crude product was purified by silica gel column chromatography with hexane/EtOAc 4:1

Sources & evidence

ORD record
ord-59c7cc6354eb48339556a2aec748741f
Source dataset
uspto-grants-2000_08
Patent number
US06107342

Reaction notes

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