Dimethylformamide → (1S,6R)-tert-butyl 8-(3-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylate

HRID 2175003Notes

Reaction equation

HRID 2175003 reaction equation
[F:1][C:2]1[C:3]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[C@H:27]12[NH:34][CH2:33][C@H:32]1[CH2:31][CH2:30][N:29]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:28]2>C(Cl)Cl>[F:1][C:2]1[C:3]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([N:34]1[C@H:27]2[C@H:32]([CH2:31][CH2:30][N:29]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:28]2)[CH2:33]1)=[O:7]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 16099093(1S,6R)-3-Boc-3,8-diazabicyclo[4.2.0]octaneHCID 670865493-Fluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid

Product 1

HCID 67086535(1S,6R)-tert-butyl 8-(3-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoyl)-3,8-diazabicyclo[4.2.0]octane-3-carboxylateYield 125.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To 3-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid (390 mg, 1.9 mmol) in CH2Cl2 (18 mL) at 0° C. was added DMF (15 μL, 0.2 mmol) and oxalyl chloride (190 μL, 2.3 mmol). After 20 min, the 0° C. ice bath was removed and the reaction allowed to warm to rt. After 30 min the mixture was concentrated, diluted with CH2Cl2 (9 mL) and added to (1S,6R)-tert-butyl 3,8-diazabicyclo[4.2.0]octane-3-carboxylate (260 mg, 1.3 mmol) in CH2Cl2 (9 mL) and TEA (390 μL, 2.9 mmol). After judged complete by TLC and LC-MS, the reaction was diluted further with CH2Cl2 and washed with 1 N KHSO4. The aqueous layer was with CH2Cl2. The combined organics were dried (Na2SO4) to give a yellow foam. Purification via silica gel using 40-100% EtOAc in hexanes gave 656 mg (86%) of the title compound as a colorless oil. MS (ESI) mass calcd. C20H24FN5O3, 401.44; m/z found 346.0 [M−C(CH3)3]+.

Workup

  1. customthe 0° C. ice bath was removed
  2. concentrationAfter 30 min the mixture was concentrated
  3. additiondiluted with CH2Cl2 (9 mL)
  4. washwashed with 1 N KHSO4
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. customto give a yellow foam
  7. customPurification via silica gel using 40-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-19bab2e795474f1cbd026c7ad7d678f3
Source dataset
uspto-grants-2015_06
Patent number
US09062044B2

Reaction notes

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