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(2-Bromo-Pyridin-3-Yl)-Carbamic Acid Tert-Butyl Ester → Tert-butyl 2-(hydroxy(1-(3-(trifluoromethyl)phenyl)cyclobutyl)methyl)-pyridin-3-ylcarbamate

HRID 1620996
Notes
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Reaction equation

HRID 1620996 reaction equation
Br[C:2]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[F:21][C:22]([F:36])([F:35])[C:23]1[CH:24]=[C:25]([C:29]2([CH:33]=[O:34])[CH2:32][CH2:31][CH2:30]2)[CH:26]=[CH:27][CH:28]=1>C1COCC1>[OH:34][CH:33]([C:29]1([C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([C:22]([F:21])([F:35])[F:36])[CH:24]=2)[CH2:30][CH2:31][CH2:32]1)[C:2]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][CH:5]=[CH:4][N:3]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 14177127(2-Bromo-Pyridin-3-Yl)-Carbamic Acid Tert-Butyl EsterHCID 895247361-(3-(Trifluoromethyl)phenyl)cyclobutanecarbaldehydeHCID 178418339Butyllithium

Product 1

HCID 89524814Tert-butyl 2-(hydroxy(1-(3-(trifluoromethyl)phenyl)cyclobutyl)methyl)-pyridin-3-ylcarbamate

Reagents, catalysts & solvents 1

HCID 8028
Tetrahydrofuran
Solvent
2×

Conditions

Temperature
-78 °C

Procedure

To a solution of Example 120A (400 mg, 1.465 mmol) in THF (5 mL) was added n-BuLi (3.08 mmol) at −78° C. The resulting solution was stirred at about −78° C. for about 1 hour and then a solution of Example 120C (365 mg, 1.611 mmol) in 10 mL of THF was added. The temperature was warmed to room temperature, stirred for another 1 hour, quenched with 10 mL of water, and extracted with ethyl acetate. The organic layer was washed with brine, and the combined organic phases were dried over sodium sulfate, filtered, and concentrated to give the desired crude product, which was used for next step without further purification. LC-MS: m/z (M+H) 439.

Workup

  1. temperatureThe temperature was warmed to room temperature
  2. stirringstirred for another 1 hour
  3. customquenched with 10 mL of water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialthe combined organic phases were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4e1f97c4296c4a69bf136b31f4d6e16d
Source dataset
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08772500B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes