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

HRID 1474699Notes

Reaction equation

HRID 1474699 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11].[Cl:14][C:15]1[CH:16]=[N:17][C:18]([N:21]2[CH2:26][CH2:25][CH:24]([C@H:27]3[CH2:29][C@H:28]3[CH2:30][CH2:31]O)[CH2:23][CH2:22]2)=[N:19][CH:20]=1.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>[Cl:14][C:15]1[CH:16]=[N:17][C:18]([N:21]2[CH2:26][CH2:25][CH:24]([C@H:27]3[CH2:29][C@H:28]3[CH2:30][CH2:31][O:8][C:6]3[CH:5]=[CH:4][C:3]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:2]([F:1])[CH:7]=3)[CH2:23][CH2:22]2)=[N:19][CH:20]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 581286112-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanolHCID 58415153Methyl 2-(2-Fluoro-4-hydroxyphenyl)acetate

Product 1

HCID 89583871Methyl [4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of methyl (2-fluoro-4-hydroxyphenyl)acetate (1.3 g, 4.61 mmol) in 15 ml anhydrous dichloromethane at RT was added a solution of 2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (1.02 g, 1.70 mmol) in 5 ml of anhydrous dichloromethane, followed by triphenylphosphine (polymer-bound, 3.63 g, 10.5 mmol) and di-tert-butyl azodicarboxylate (2.13 g, 9.23 mmol). The mixture was stirred at RT for 3 hours, filtered through Celite and concentrated. The residue was purified by column chromatography on silica gel (Biotage 100 g) using a gradient eluent of 0-50% ethyl acetate in hexanes (1500 ml) to afford the title compound. LC/MS (m/z) 448.2 (M+H)+.

Workup

  1. filtrationfiltered through Celite
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography on silica gel (Biotage 100 g)

Sources & evidence

ORD record
ord-187aa1c6fb4543f9b11c7b40c0882a7e
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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