Sodium Thiosulfate → 3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester

HRID 519134Notes

Reaction equation

HRID 519134 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([CH3:29])([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][CH:26]=2)[O:23][CH2:22][C:21]2[N:16]3[C@H:17]([CH3:28])[C:18](=[O:27])[NH:19][N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br-:30].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.[O-]S([O-])(=S)=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CO>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[Br:30])[O:23][CH2:22][C:21]2[N:16]3[C@H:17]([CH3:28])[C:18](=[O:27])[NH:19][N:20]=2)([CH3:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 24477Sodium ThiosulfateHCID 516892Sodium BicarbonateHCID 23500184Tetra-n-butylammonium tribromideHCID 86727522HCID 86727522, compound

Product 1

HCID 867275233-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl esterYield 84%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-methyl-3-((R)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (20 g, 49.8 mmol) in CH2Cl2 (240 mL) and MeOH (120 mL) was added tetra-n-butylammonium tribromide (24.02 g, 49.8 mmol) in portions and the reaction mixture was stirred for 4 h. Saturated aqueous Na2S2O3 solution (100 mL) and saturated aqueous NaHCO3 solution (50 mL) was added to quench the reaction. The aqueous solution was extracted with CH2Cl2 (3×50 mL). The combined organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether) to give 3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (20 g, 84%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.68 (brs, 1H), 7.14 (s, 1H), 4.63-4.57 (m, 1H), 4.56-4.45 (m, 2H), 4.34 (s, 1H), 4.08-4.01 (m, 2H), 3.96-3.90 (m, 2H), 1.62 (s, 3H), 1.51-1.45 (m, 12H). LCMS (Table 1, Method 25) Rt=0.867 min; MS m/z: 482 [M+H+2]+& 480 [M+H]+. SFC (Table 1, Method 31) Rt=5.402 min.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionThe aqueous solution was extracted with CH2Cl2 (3×50 mL)
  4. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-5ac8ef7258dd498f98f781cefb9a069d
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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