Diiodomethane → HCID 76567954, compound

HRID 1728109Notes

Reaction equation

HRID 1728109 reaction equation
C(I)I.[Zn](CC)[CH2:5]C.C(OC([N:16]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([Cl:41])[CH:39]=2)[C:18]2([CH:23]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=3)[CH2:22][C:21](=[O:31])[NH:20][CH:19]2[C:32]([CH3:34])=[CH2:33])[C:17]1=[O:42])=O)(C)(C)C>C1(C)C=CC=CC=1>[Cl:41][C:38]1[CH:39]=[C:40]2[NH:16][C:17](=[O:42])[C:18]3([CH:23]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=4)[CH2:22][C:21](=[O:31])[NH:20][CH:19]3[C:32]3([CH3:33])[CH2:5][CH2:34]3)[C:35]2=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 6346DiiodomethaneHCID 76567940HCID 76567940, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 76567954HCID 76567954, compoundYield 84.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

To a solution of CH2I2 (1.2 g, 4.6 mmol) in anhydrous toluene (5 mL) under Argon at 0° C. was added a toluene solution of Et2Zn (1.1M, 3.3 ml, 3.67 mmol). The mixture was stirred for 15 min, then a toluene solution (10 mL) of racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-isopropenyl-2,6′-dioxospiro[indole-3,3′-piperidine]-1-carboxylic acid tert-butyl ester (230 mg, 0.46 mmol) prepared in example 171a was added. The reaction mixture was stirred at room temperature for 3 h, then quenched with aqueous saturated NH4Cl (20 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over Na2SO4 and concentrated to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chloro-phenyl)-2′-(1-methyl-cyclopropyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (162 mg). Then racemic (2′R,3R,4′S)-6-chloro-4′-(3-chloro-phenyl)-2′-(1-methyl-cyclopropyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione by chiral SFC to give chiral (2′R,3R,4′S)-6-chloro-4′-(3-chloro-phenyl)-2′-(1-methyl-cyclopropyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (50 mg).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 h
  2. customquenched with aqueous saturated NH4Cl (20 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-143e9c14a18340259ef6b6471f8f204c
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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