Triphenylphosphine → Diethyl 1-((3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl)methyl)-3-iodo-1H-pyrazole-4,5-dicarboxylate

HRID 920842Notes

Reaction equation

HRID 920842 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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]1[CH2:56][O:55][C:54]([CH3:58])([CH3:57])[N:53]1[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60]>C1COCC1>[C:62]([O:61][C:59]([N:53]1[CH:52]([CH2:51][N:37]2[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]2)[CH2:56][O:55][C:54]1([CH3:57])[CH3:58])=[O:60])([CH3:65])([CH3:63])[CH3:64]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 14409442Tert-butyl 4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylateHCID 178470428HCID 178470428, compound

Product 1

HCID 118062571Diethyl 1-((3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl)methyl)-3-iodo-1H-pyrazole-4,5-dicarboxylateYield 71.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of triphenylphosphine (5.84 g, 22.25 mmol) in THF (20 mL) was added DIAD (4.50 g 22.25 mmol) dropwise at 0° C. and the resulting solution was stirred for 15 min. Intermediate 104C (3.0 g, 8.90 mmol) in THF (20 mL) was added slowly at 0° C. and stirred at room temperature for 45 min. Intermediate tert-butyl 4-(hydroxymethyl)-2,2-dimethyloxazolidine-3-carboxylate (2.470 g, 10.68 mmol) in THF (20 mL) was added at 0° C. and resulting solution was stirred at room temperature overnight. The volatiles were removed under reduced pressure and the crude compound was purified by silica gel chromatography (40 g REDISEP® column, eluting with 10-13% ethyl acetate in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 351A (3.5 g, 58.5%) as a pale yellow oil. MS(ES): m/z=552 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 4.53-4.18 (m, 6H), 3.96-3.82 (m, 2H), 1.50-1.21 (m, 2H).

Workup

  1. stirringstirred at room temperature for 45 min
  2. customresulting solution
  3. stirringwas stirred at room temperature overnight
  4. customThe volatiles were removed under reduced pressure
  5. customthe crude compound was purified by silica gel chromatography (40 g REDISEP® column, eluting with 10-13% ethyl acetate in hexanes)
  6. additionFractions containing the product
  7. customevaporated

Sources & evidence

ORD record
ord-64696827eb9f426ea654cadd999c8542
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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