Triphenylphosphine → Diethyl 1-(2-((tert-butoxycarbonyl)amino)propyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

HRID 920816Notes

Reaction equation

HRID 920816 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[CH2:51][CH:52]([NH:54][C:55](=[O:61])[O:56][C:57]([CH3:60])([CH3:59])[CH3:58])[CH3:53]>C1COCC1.C(OCC)(=O)C>[C:57]([O:56][C:55]([NH:54][CH:52]([CH3:53])[CH2:51][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:61])([CH3:60])([CH3:59])[CH3:58]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 545701tert-butyl N-(1-hydroxypropan-2-yl)carbamateHCID 5363146Diisopropyl azodicarboxylateHCID 178470428HCID 178470428, compound

Product 1

HCID 118061851Diethyl 1-(2-((tert-butoxycarbonyl)amino)propyl)-3-iodo-1H-pyrazole-4,5-dicarboxylateYield 59.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of PPh3 (12.41 g, 47.3 mmol) in THF (100 mL) was added DIAD (9.20 mL, 47.3 mmol) at 10° C. and allowed to stir at 0° C. for 0.5 h. Intermediate 104C (8.0 g, 23.66 mmol) was added as a solution in THF (10 mL) at 0° C. and stirred at RT for 45 min. The reaction mixture was cooled again to 0° C. and tert-butyl (1-hydroxypropan-2-yl)carbamate (5.39 g, 30.8 mmol) was added as a solution in THF (10 mL) and the mixture was stirred at RT for 16 h. The reaction mixture was diluted with ethyl acetate (100 mL), washed with water and brine. The organic layer was dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (40 g REDISEP® column, eluting with 15% EtOAc in hexane). Fractions containing the product were combined and evaporated to afford the Intermediate 340A as a brown liquid (7.0 g) contaminated with impurities arising from the coupling reagents. MS(ES): m/z=496 [M+H]+. The crude intermediate was taken to the next step without further purification.

Workup

  1. stirringstirred at RT for 45 min
  2. temperatureThe reaction mixture was cooled again to 0° C.
  3. stirringthe mixture was stirred at RT for 16 h
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under reduced pressure
  8. customThe crude compound was purified by silica gel chromatography (40 g REDISEP® column, eluting with 15% EtOAc in hexane)
  9. additionFractions containing the product
  10. customevaporated

Sources & evidence

ORD record
ord-ec195fa713144973b97502d5a20ae4f1
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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