Diiodomethane → HCID 86691264, compound

HRID 2037289Notes

Reaction equation

HRID 2037289 reaction equation
F[C:2](F)(F)C(O)=O.C([Zn]CC)C.ICI.[CH:16]1[C:28]2[CH:27]([CH2:29][O:30][C:31]([NH:33][C@@:34]3([C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:39][C:38](=[CH2:40])[C@@H:37]4[C@H:35]3[C@H:36]4[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[O:32])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]=2[CH:19]=[CH:18][CH:17]=1>ClCCl>[CH:25]1[C:26]2[CH:27]([CH2:29][O:30][C:31]([NH:33][C@@:34]3([C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:39][C:38]4([CH2:2][CH2:40]4)[C@@H:37]4[C@H:35]3[C@H:36]4[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[O:32])[C:28]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:21]=2[CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 6422Trifluoroacetic acidHCID 86691262HCID 86691262, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 86691264HCID 86691264, compoundYield 91.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
2.5 °C

Procedure

Add a solution of trifluoroacetic acid (2.66 g, 23.3 mmol) in dichloromethane (11.7 mL) dropwise over 5 minutes to a stirred solution of diethyl zinc 1M in heptanes (23.3 mL, 23.3 mmol) in dichloromethane (11.7 mL) cooled to 0-5° C. under nitrogen (exothermic reaction). After 10 minutes, add a solution of diiodomethane (6.25 g, 23.3 mmol) in dichloromethane (11.7 mL). After 10 minutes, add a solution of diethyl (1S,2S,5R,6S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-methylene-bicyclo[3.1.0]hexane-2,6-dicarboxylate (3.70 g, 7.8 mmol) in dichloromethane (11.7 mL). After 2 hours at 0° C., allow to warm to room temperature and stir for 16 hours. Quench the reaction mixture with cold 0.5M hydrochloric acid (50 mL) and dichloromethane (20 mL) and stir vigorously. Separate the dichloromethane layer via a hydrophobic frit and then evaporate to a pale yellow oil. Purify by flash chromatography eluting with ethyl acetate:iso-hexane (10:90 to 20:80) to give a colorless oil (3.49 g). Repurify by flash chromatography eluting with ethyl acetate:iso-hexane (20:80) taking the centre cut fractions to give a colorless foam of title compound (2.12 g, 56%). MS (m/z): 490 (M+1). A second lot of product from the less pure fractions is obtained by repeated chromatography (363 mg, additional 9%).

Workup

  1. waitAfter 10 minutes
  2. waitAfter 2 hours at 0° C.
  3. temperatureto warm to room temperature
  4. customQuench the reaction mixture with cold 0.5M hydrochloric acid (50 mL) and dichloromethane (20 mL)
  5. stirringstir vigorously
  6. customSeparate the dichloromethane layer via a hydrophobic frit
  7. customevaporate to a pale yellow oil
  8. customPurify by flash chromatography
  9. washeluting with ethyl acetate:iso-hexane (10:90 to 20:80)

Sources & evidence

ORD record
ord-e730bf5bddc14000988e694d3498b102
Source dataset
uspto-grants-2013_11
Patent number
US08575214B2

Reaction notes

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