Triphenylphosphine → tert-butyl (2S)-2-[(4-bromo-1H-pyrazol-1-yl)methyl]morpholine-4-carboxylate

HRID 595205Notes

Reaction equation

HRID 595205 reaction equation
O[CH2:2][C@H:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.[Br:16][C:17]1[CH:18]=[N:19][NH:20][CH:21]=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCCC1>[Br:16][C:17]1[CH:18]=[N:19][N:20]([CH2:2][C@H:3]2[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[CH2:4]2)[CH:21]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 163754-BromopyrazoleHCID 97268Di-tert-butyl azodicarboxylateHCID 1512577tert-Butyl (2S)-2-(hydroxymethyl)morpholine-4-carboxylate

Product 1

HCID 118216471tert-butyl (2S)-2-[(4-bromo-1H-pyrazol-1-yl)methyl]morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrahydrofuran was added to a mixture of (S)-tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate (250 mg, 1.15 mmol), 4-bromo-1H-pyrazole (186 mg, 1.27 mmol), di-tert-butyl azodicarboxylate (530 mg, 2.30 mmol), and triphenylphosphine resin (3 mmol/g loading, 601 mg, 2.30 mmol) under argon. The resulting suspension was stirred for 8 days and then filtered through CELITE. The supernatant was concentrated under reduced pressure, and the residue was purified by chromatography on silica gel (5-100% ethyl acetate/hexanes) to afford tert-butyl (2S)-2-[(4-bromo-1H-pyrazol-1-yl)methyl]morpholine-4-carboxylate. ESI calc'd. for C9H13BrN3O3 [M+H t-Bu]+ 289 and 291. found 289 and 291. 1H NMR (500 MHz, CDCl3) δ 7.49 (s, 1H), 7.46 (s, 1H), 4.22-4.08 (m, 2H), 4.04-3.78 (m, 3H), 3.76-3.69 (br s, 1H), 3.52-3.46 (m, 1H), 2.99-2.82 (br s, 1H), 2.63-2.51 (br s, 1H), 1.45 (s, 9H).

Workup

  1. filtrationfiltered through CELITE
  2. concentrationThe supernatant was concentrated under reduced pressure
  3. customthe residue was purified by chromatography on silica gel (5-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0692eef4430b409396bf6a991c428fd0
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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