(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidine → (R)-tert-butyl-(4-(N-1,2,4-thiadiazol-5-ylsulfamoyl)phenyl)pyrrolidin-3-ylcarbamate

HRID 1696172Notes

Reaction equation

HRID 1696172 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:16][N:15]=[CH:14][N:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH:17]1[CH2:21][CH2:20][C@@H:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:25]([O:24][C:23](=[O:29])[N:22]([C:2]1[CH:7]=[CH:6][C:5]([S:8](=[O:10])(=[O:9])[NH:11][C:12]2[S:16][N:15]=[CH:14][N:13]=2)=[CH:4][CH:3]=1)[C@@H:19]1[CH2:20][CH2:21][NH:17][CH2:18]1)([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 536276064-bromo-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Product 1

HCID 67093238(R)-tert-butyl-(4-(N-1,2,4-thiadiazol-5-ylsulfamoyl)phenyl)pyrrolidin-3-ylcarbamateYield 21%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Prepared using general procedure 74. The reaction was set up with 4-bromo-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (750 mg, 2.34 mmol), (R)-tert-butyl pyrrolidin-3-ylcarbamate (436 mg, 2.34 mmol), Pd2(dba)3 (64 mg, 0.07 mmol), biphenyl-2-yldi-tert-butylphosphine (84 mg, 0.28 mmol), sodium tert-butoxide (630 mg, 6.6 mmol), and toluene (6.0 mL). Purification via silica gel chromatography using 10% MeOH in CH2Cl2 gave the desired pyrrolidine as an orange solid (213 mg, 0.49 mmol, 21% yield). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=326.3; tR=1.39 min.

Workup

  1. customPrepared
  2. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-92e20c7d2ce0466abf02059c9dca73f0
Source dataset
uspto-grants-2012_04
Patent number
US08163720B2

Reaction notes

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