Triphenylphosphine → Diethyl1-(2-((tert-butoxycarbonyl)amino)-2-cyclopropylethyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

HRID 920827Notes

Reaction equation

HRID 920827 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.[CH:50]1([CH:53]([NH:56][C:57](=[O:63])[O:58][C:59]([CH3:62])([CH3:61])[CH3:60])[CH2:54]O)[CH2:52][CH2:51]1>C1COCC1.CCOC(C)=O>[CH2:43]([O:42][C:40]([C:39]1[C:35]([I:34])=[N:36][N:37]([CH2:54][CH:53]([NH:56][C:57]([O:58][C:59]([CH3:60])([CH3:62])[CH3:61])=[O:63])[CH:50]2[CH2:51][CH2:52]2)[C:38]=1[C:45]([O:47][CH2:48][CH3:49])=[O:46])=[O:41])[CH3:44]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 66707724Carbamic acid, N-(1-cyclopropyl-2-hydroxyethyl)-, 1,1-dimethylethyl esterHCID 178470428HCID 178470428, compound

Product 1

HCID 118062403Diethyl1-(2-((tert-butoxycarbonyl)amino)-2-cyclopropylethyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of PPh3 (15.52 g, 59.2 mmol) in THF (40.0 mL) cooled to −10° C. was added DIAD (11.50 mL, 59.2 mmol) and the resulting solution stirred at 0° C. for 0.5 h. Intermediate 104C (10 g, 29.6 mmol) was added as a solution in THF (10 mL) at 0° C. and stirred at RT for 45 min. A solution of Intermediate 348A (7.74 g, 38.5 mmol) in THF (10 mL) at was added at 0° C. and the reaction mixture was allowed to stir at RT for 16 h. The reaction mixture was diluted with EtOAc (50 mL) washed with water and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (120 g REDISEP® column, eluting with 15% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 348B along with impurities arising from the coupling reagents (8.01 g, 84%); the crude material was taken to the next step without further purification. MS(ES): m/z=522 [M+H]+.

Workup

  1. stirringstirred at RT for 45 min
  2. stirringto stir at RT for 16 h
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude compound was purified by silica gel chromatography (120 g REDISEP® column, eluting with 15% EtOAc in hexanes)
  7. additionFractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-366afc331020412e96c2e303a9f2351a
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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