Triphenylphosphine → Diethyl 1-((3R,4S)-4-((tert-butoxycarbonyl)amino)tetrahydrofuran-3-yl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

HRID 920848Notes

Reaction equation

HRID 920848 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[I:34][C:35]1[C:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[C:38]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[NH:37][N:36]=1.O[C@H:51]1[CH2:55][O:54][CH2:53][C@@H:52]1[NH:56][C:57](=[O:63])[O:58][C:59]([CH3:62])([CH3:61])[CH3:60]>C1COCC1>[C:59]([O:58][C:57]([NH:56][C@@H:52]1[CH2:53][O:54][CH2:55][C@@H:51]1[N:37]1[C:38]([C:45]([O:47][CH2:48][CH3:49])=[O:46])=[C:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])[C:35]([I:34])=[N:36]1)=[O:63])([CH3:62])([CH3:60])[CH3:61]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 20792948tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamateHCID 178470428HCID 178470428, compound

Product 1

HCID 118062353Diethyl 1-((3R,4S)-4-((tert-butoxycarbonyl)amino)tetrahydrofuran-3-yl)-3-iodo-1H-pyrazole-4,5-dicarboxylateYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of PPh3 (2.72 g, 10.35 mmol) in THF (10 mL) at 0° C. was added DIAD (2.013 mL, 10.35 mmol) dropwise and stirred for 15 min. A solution of Intermediate 104C (1.4 g, 4.14 mmol) in THF (10 mL) was added to the above reaction mixture and was stirred at 0° C. for 45 min. A solution of tert-butyl ((3S,4R)-4-hydroxytetrahydrofuran-3-yl)carbamate (1.683 g, 8.28 mmol) in THF (10 mL) was added dropwise at 0° C. and the reaction mixture was stirred at RT for 12 h. The reaction mixture was then concentrated and the crude compound was purified by silica gel chromatography (24 g REDISEP® column, eluting with 30% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 352A (1.7 g, 81%) as a white solid. MS(ES): m/z=522 [M−H]+; The crude product was taken to the next step without further purification.

Workup

  1. stirringwas stirred at 0° C. for 45 min
  2. stirringthe reaction mixture was stirred at RT for 12 h
  3. concentrationThe reaction mixture was then concentrated
  4. customthe crude compound was purified by silica gel chromatography (24 g REDISEP® column, eluting with 30% EtOAc in hexanes)
  5. additionFractions containing the product
  6. customevaporated

Sources & evidence

ORD record
ord-d5a5d9932bd24180ac4711bbe3a5ffbc
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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