Dichloromethane → Tert-butyl {(3r)-1-[4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-2-formylphenyl]pyrrolidin-3-yl}carbamate

HRID 724595Notes

Reaction equation

HRID 724595 reaction equation
[CH:1]([C:3]1[CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:6]=[CH:5][C:4]=1[N:18]1[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:19]1)=[O:2].C(=O)([O-])[O-].[K+].[K+].[C:37]([N:41]1[C:45](=[O:46])[CH:44]=[C:43](Cl)[S:42]1(=[O:49])=[O:48])([CH3:40])([CH3:39])[CH3:38].ClCCl>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:37]([N:41]1[C:45](=[O:46])[CH:44]=[C:43]([C:7]2[CH:6]=[CH:5][C:4]([N:18]3[CH2:22][CH2:21][C@@H:20]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:19]3)=[C:3]([CH:1]=[O:2])[CH:8]=2)[S:42]1(=[O:49])=[O:48])([CH3:40])([CH3:39])[CH3:38]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 218786382-Tert-butyl-5-chloro-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trioneHCID 58746884Tert-butyl {(3r)-1-[2-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrrolidin-3-yl}carbamate

Product 1

HCID 58746896Tert-butyl {(3r)-1-[4-(2-tert-butyl-1,1-dioxido-3-oxo-2,3-dihydroisothiazol-5-yl)-2-formylphenyl]pyrrolidin-3-yl}carbamateYield 73%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Boronic ester 22-B in dioxane (1 mL) was treated with potassium carbonate (124 mg, 0.901 mmol), heterocycle 9-A (48 mg, 0.21 mmol) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (17.6 mg, 0.0216 mmol). The solution was degassed, placed under nitrogen and heated to 80° C. for 48 hours. The solution was allowed to cool to ambient temperature, diluted with ethyl acetate (10 mL) and washed with water (10 mL). The organics were separated, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography (30 ethyl acetate/hexanes) to afford a yellow solid 22-C (63 mg, 73%). 1H NMR (500 MHz, CD3OD): δ 10.05 (s, 1H), 8.25 (d, J=1.95 Hz, 1H), 7.87 (dd, J=11.22 Hz, 1H), 7.06 (d, J=9.27 Hz, 1H), 6.84 (s, 1H), 4.24 (m, 1H), 3.70 (m, 2H), 3.65 (m, 1H), 3.19 (m, 1H), 2.28 (m, 1H), 2.26 (m, 1H), 1.72 (s, 9H), 1.46 (s, 9H); LCMS found for C23H31N3O6S (M+H)+: m/z=478.

Workup

  1. customThe solution was degassed
  2. temperatureto cool to ambient temperature
  3. additiondiluted with ethyl acetate (10 mL)
  4. washwashed with water (10 mL)
  5. customThe organics were separated
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (30 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-149e77a9b02f4303aa9d4008cbe1426f
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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