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

HRID 1474720Notes

Reaction equation

HRID 1474720 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][OH:20])[CH2:11][CH2:10]2)=[N:7][CH:8]=1.[Br:21][C:22]1[C:27]([F:28])=[CH:26][C:25](O)=[CH:24][C:23]=1[F:30].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[Br:21][C:22]1[C:27]([F:28])=[CH:26][C:25]([O:20][CH2:19][CH2:18][C@@H:16]2[CH2:17][C@@H:15]2[CH:12]2[CH2:13][CH2:14][N:9]([C:6]3[N:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][N:5]=3)[CH2:10][CH2:11]2)=[CH:24][C:23]=1[F:30]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 71720274-Bromo-3,5-difluorophenolHCID 89581860HCID 89581860, compound

Product 1

HCID 1176783652-(4-((1R,2S)-2-(2-(4-bromo-3,5-difluorophenoxy)ethyl)cyclopropyl)piperidin-1-yl)-5-methoxypyrimidineYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-((1S,2R)-2-(1-(5-methoxypyrimidin-2-yl)piperidin-4-yl)cyclopropyl)ethanol (1.4 g, 5.05 mmol), 4-bromo-3,5-difluorophenol (1.26 g, 6.06 mmol) and triphenylphosphine (1.98 g, 7.57 mmol) were dissolved in dichloromethane (25 ml). The mixture was stirred at RT under N2 for 5 min and diisopropyl azodicarboxylate (1.53 g, 7.57 mmol) added. The mixture was stirred at RT overnight. The mixture was diluted with DCM (50 ml), washed with 0.5 N NaOH (50 ml), brine, dried over sodium sulfate and the volatiles removed in vacuo. The residue was purified by silica gel column chromatography (50 g SNAP, 10˜40% EtOAc in hexane) to afford 1.86 g (79%) of the titled compound. LC/MS (m/z): 469 (M+H)+. Rf was 0.3 @ 30% EtOAc in hexanes (blue spot on CAM stain)

Workup

  1. stirringThe mixture was stirred at RT overnight
  2. washwashed with 0.5 N NaOH (50 ml), brine
  3. dry with materialdried over sodium sulfate
  4. customthe volatiles removed in vacuo
  5. customThe residue was purified by silica gel column chromatography (50 g SNAP, 10˜40% EtOAc in hexane)

Sources & evidence

ORD record
ord-304beaa53774439eb4ce4489faf47e50
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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