Triethylamine → (2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

HRID 474107Notes

Reaction equation

HRID 474107 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:21]S(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)([CH3:20])[CH2:9][O:10][C@@:11]([CH3:19])([C:15]([F:18])([F:17])[F:16])[C:12]([NH2:14])=O)[C:5]([F:34])=[CH:4][CH:3]=1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:20])[CH2:9][O:10][C@@:11]([CH3:19])([C:15]([F:18])([F:17])[F:16])[C:12]([NH2:14])=[N:21]2)[C:5]([F:34])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 9845Trifluoroacetic anhydride2×HCID 86668077(R)-2-[(R)-2-(6-Bromo-3-fluoro-pyridin-2-yl)-2-(4-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionamide

Product 1

HCID 86668039(2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamineYield 148.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

A suspension of (R)-2-[(R)-2-(6-bromo-3-fluoro-pyridin-2-yl)-2-(4-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionamide (8.43 g, 14.70 mmol) and triethylamine (5.12 ml, 36.8 mmol) in 85 ml DCM was cooled to 0-5° C. Trifluoroacetic anhydride (2.49 ml, 17.64 mmol) was added dropwise over 30 min. Additional triethylamine (1.54 ml, 11.07 mmol) and trifluoroacetic anhydride (0.75 ml, 5.29 mmol) were added to complete the reaction. The reaction mixture was quenched by addition of 14 ml aqueous ammonia (25%) and 14 ml water. The emulsion was stirred for 15 min, more water and DCM were added and the layers were separated. The organic layer was dried with MgSO4 H2O, filtered and evaporated. Purification by column chromatography on a silica gel (hexanes/10-25% EtOAc) gave 8.09 g of the title compound as a yellow resin.

Workup

  1. customthe reaction
  2. customThe reaction mixture was quenched by addition of 14 ml aqueous ammonia (25%) and 14 ml water
  3. additionmore water and DCM were added
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried with MgSO4 H2O
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by column chromatography on a silica gel (hexanes/10-25% EtOAc)

Sources & evidence

ORD record
ord-6d652aedb6f546f3a7955f2460a84b8c
Source dataset
uspto-grants-2014_01
Patent number
US08637508B2

Reaction notes

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