Di-tert-butyl azodicarboxylate → 1-methylcyclopropyl 4-[(1R,2S)-2-{2-[3-fluoro-4-(2-methoxy-2-oxoethyl)phenoxy]ethyl}cyclopropyl]piperidine-1-carboxylate

HRID 1850760Notes

Reaction equation

HRID 1850760 reaction equation
[OH:1][CH2:2][CH2:3][C@@H:4]1[CH2:6][C@@H:5]1[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]2([CH3:19])[CH2:18][CH2:17]2)=[O:14])[CH2:9][CH2:8]1.[F:20][C:21]1[CH:26]=[C:25](O)[CH:24]=[CH:23][C:22]=1[CH2:28][C:29]([O:31][CH3:32])=[O:30].N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:20][C:21]1[CH:26]=[C:25]([CH:24]=[CH:23][C:22]=1[CH2:28][C:29]([O:31][CH3:32])=[O:30])[O:1][CH2:2][CH2:3][C@@H:4]1[CH2:6][C@@H:5]1[CH:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]2([CH3:19])[CH2:18][CH2:17]2)=[O:14])[CH2:9][CH2:8]1

Participants

6

Reactant 3

HCID 97268Di-tert-butyl azodicarboxylateHCID 58415153Methyl 2-(2-Fluoro-4-hydroxyphenyl)acetateHCID 708189561-methylcyclopropyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl)piperidine-1-carboxylate2×

Product 1

HCID 867111961-methylcyclopropyl 4-[(1R,2S)-2-{2-[3-fluoro-4-(2-methoxy-2-oxoethyl)phenoxy]ethyl}cyclopropyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 11776TriphenylphosphineSolvent

Procedure

To a solution of 1-methylcyclopropyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidine-1-carboxylate (Intermediate 9, 0.484 g, 1.81 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of methyl (2-fluoro-4-hydroxyphenyl)acetate (0.400 g, 2.17 mmol) in 10 ml anhydrous dichloromethane, triphenylphosphine, polymer-bound (1.42 g, 4.10 mmol), and di-tert-butyl azodicarboxylate (0.834 g, 3.61 mmol). The reaction mixture was stirred at RT for 3 hours. It was filtered by Celite and concentrated. The residue was purified on Biotage column (50 g silica gel) using a gradient eluent of 0-50% ethyl acetate in hexanes (1000 ml) to afford the title compound. LC/MS (m/z) 434.2 (M+H)+.

Workup

  1. filtrationIt was filtered by Celite
  2. concentrationconcentrated
  3. customThe residue was purified on Biotage column (50 g silica gel)

Sources & evidence

ORD record
ord-89ed6c2a51cd4cd9a9da0b2a096df3fd
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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