Triethylamine → [(RS)-1-(6-Bromo-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester

HRID 538315Notes

Reaction equation

HRID 538315 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Br:27])[N:22]=1)([CH3:20])[CH2:9][O:10][C@@:11]([C:17](=O)[NH2:18])([CH3:16])[C:12]([F:15])([F:14])[F:13])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.N.CO>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Br:27])[N:22]=1)([CH3:20])[CH2:9][O:10][C@@:11]([C:17]#[N:18])([CH3:16])[C:12]([F:14])([F:15])[F:13])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 21705897Ammonia methanolHCID 86715546[(RS)-1-(6-Bromo-pyridin-2-yl)-2-((R)-1-carbamoyl-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 86715548[(RS)-1-(6-Bromo-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 10340Sodium CarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To an at 0° C. per cooled solution of [(RS)-1-(6-bromo-pyridin-2-yl)-2-((R)-1-carbamoyl-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester (2.18 g, 4.64 mmol) and NEt3 (1.615 ml, 1.173 g, 11.59 mmol) in DCM (30 ml) was added dropwise TFAA (0.773 ml, 1.168 g, 5.56 mmol). After stirring for 5 min at 0° C., then for 1 h at rt the reaction mixture was diluted with sat. aq. Na2CO3 soln. and with DCM. The phases were separated and the aq. phase was twice reextracted with DCM. The combined org. phases were dried over Na2SO4, filtered and concentrated to leave a pale yellow oil which was stirred with 7N NH3/MeOH for 5 min. The mixture was evaporated to dryness and purified by flash chromatography (cyclohexane: EtOAc 0-3 min 100:0, 3-35 min 65:35) to yield the title compound as a clear oil.

Workup

  1. customThe phases were separated
  2. dry with materialphases were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto leave a pale yellow oil which
  6. customThe mixture was evaporated to dryness
  7. custompurified by flash chromatography (cyclohexane: EtOAc 0-3 min 100:0, 3-35 min 65:35)

Sources & evidence

ORD record
ord-68b2254f6ed347bbb1d52abff396f6ed
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

Loading…