Triphenylphosphine → Methyl [4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetate

HRID 1474710Notes

Reaction equation

HRID 1474710 reaction equation
[CH2:1]([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][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][OH:29])=[C:23]([F:30])[CH:22]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].N1(C(=O)CC2C(F)=C[C:40]([OH:44])=CC=2F)CCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:10][CH2:11][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([CH2:27][C:28]([O:44][CH3:40])=[O:29])=[C:23]([F:30])[CH:22]=3)[CH2:13][CH2:14]2)=[N:7][CH:8]=1)[CH3:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 895828981-(Azetidin-1-yl)-2-(2,6-difluoro-4-hydroxyphenyl)ethanoneHCID 1176782312-[4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]ethanol

Product 1

HCID 117684491Methyl [4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-[4-(2-{(1S,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]ethanol (0.200 g, 0.726 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of 1-(azetidin-1-yl)-2-(2,6-difluoro-4-hydroxyphenyl) ethanone (0.160 g, 0.871 mmol) in 5 ml anhydrous dichloromethane. Triphenylphosphine, polymer-bound (0.571 g, 1.90 mmol), and di-tert-butyl azodicarboxylate (0.334 g, 1.45 mmol) was added and the slurry stirred at RT for 3 hours. The mixture was filtered through Celite and the filtrate concentrated in vacuo. The residue was purified by column chromatography on silica gel (Biotage column, 50 g) using a gradient eluent of 0-50% ethyl acetate in hexanes (700 ml) to afford the title compound. LC/MS (m/z) 442.3 (M+H)+.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationthe filtrate concentrated in vacuo
  3. customThe residue was purified by column chromatography on silica gel (Biotage column, 50 g)

Sources & evidence

ORD record
ord-23f1a77fc1df42f194529924616993ba
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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