Triphenylphosphine → 2-(4-((1R,2S)-2-(2-(4-bromo-3,5-difluorophenoxy)ethyl)cyclopropyl)piperidin-1-yl)-5-ethoxypyrimidine

HRID 1474730Notes

Reaction equation

HRID 1474730 reaction equation
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH2:15]([O:17][C:18]1[CH:19]=[N:20][C:21]([N:24]2[CH2:29][CH2:28][CH:27]([C@H:30]3[CH2:32][C@H:31]3[CH2:33][CH2:34][OH:35])[CH2:26][CH2:25]2)=[N:22][CH:23]=1)[CH3:16].[Br:36][C:37]1[C:42]([F:43])=[CH:41][C:40](O)=[CH:39][C:38]=1[F:45].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:36][C:37]1[C:42]([F:43])=[CH:41][C:40]([O:35][CH2:34][CH2:33][C@@H:31]2[CH2:32][C@@H:30]2[CH:27]2[CH2:26][CH2:25][N:24]([C:21]3[N:22]=[CH:23][C:18]([O:17][CH2:15][CH3:16])=[CH:19][N:20]=3)[CH2:29][CH2:28]2)=[CH:39][C:38]=1[F:45]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 71720274-Bromo-3,5-difluorophenolHCID 895839062-((1S,2R)-2-(1-(5-ethoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol

Product 1

HCID 1176783442-(4-((1R,2S)-2-(2-(4-bromo-3,5-difluorophenoxy)ethyl)cyclopropyl)piperidin-1-yl)-5-ethoxypyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

DIAD (2.45 mL, 12.6 mmol) was slowly added to a solution of 2-((1S,2R)-2-(1-(5-ethoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol (2.45 g, 8.41 mmol), 4-bromo-3,5-difluorophenol (1.93 g, 9.25 mmol), and triphenylphosphine (3.31 g, 12.6 mmol) in DCM (30 mL) that had been cooled to 0° C. The ice bath was removed and the resulting mixture was stirred at rt for 3 hrs. The reaction mixture was diluted with DCM (20 mL) and washed with a 2 N NaOH solution (30 mL×1). The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (KP-Sil 100 g SNAP column, Biotage system) eluting with 5-40% EtOAc:hexanes over 12 CV to afford the title compound. LC/MS (m/z): 482 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. additionThe reaction mixture was diluted with DCM (20 mL)
  3. washwashed with a 2 N NaOH solution (30 mL×1)
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (KP-Sil 100 g SNAP column, Biotage system)
  8. washeluting with 5-40% EtOAc

Sources & evidence

ORD record
ord-fbb0f8d8630c4f03902784bb81cc015c
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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