Water → (3S,5S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-5-(1-cyanocyclopropylcarbamoyl)pyrrolidin-3-yl Benzenesulfonate

HRID 1697732Notes

Reaction equation

HRID 1697732 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([N:13]3[CH2:17][C@@H:16]([OH:18])[CH2:15][C@H:14]3[C:19]([NH:21][C:22]3([C:25]#[N:26])[CH2:24][CH2:23]3)=[O:20])=[O:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:27]1([S:33](Cl)(=[O:35])=[O:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(N(CC)CC)C.O>O1CCCC1.CN(C1C=CC=CN=1)C.CO>[C:27]1([S:33]([O:18][C@H:16]2[CH2:15][C@@H:14]([C:19](=[O:20])[NH:21][C:22]3([C:25]#[N:26])[CH2:23][CH2:24]3)[N:13]([C:11]([C:8]3([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[CH2:9][CH2:10]3)=[O:12])[CH2:17]2)(=[O:35])=[O:34])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

8

Reactant 4

HCID 962WaterHCID 7369Benzenesulfonyl chlorideHCID 8471TriethylamineHCID 67278484(2S,4S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-N-(1-cyanocyclopropyl)-4-hydroxypyrrolidine-2-carboxamide

Product 1

HCID 86646867(3S,5S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-5-(1-cyanocyclopropylcarbamoyl)pyrrolidin-3-yl BenzenesulfonateYield 99.2%

Reagents, catalysts & solvents 3

HCID 218852-DimethylaminopyridineCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of (2S,4S)-1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-N-(1-cyanocyclopropyl)-4-hydroxypyrrolidine-2-carboxamide (Example 457b; 5 g) in tetrahydrofuran (22 mL) at 0-5° C., was added benzenesulfonyl chloride (2.89 g, 2.1 ml, 16.2 mmol, Eq: 1.21), dimethylaminopyridine (88.7 mg) and triethylamine (2.41 g) within 5 minutes. The mixture was stirred at 0-5° C. for 15 min, then at 22° C. for 22 hr. Water (6.7 mL) and methanol (15.6 mL) were added at 0-5° C. and the mixture was concentrated in vacuo to afford a gum. This gum was washed with methanol and dried in vacuo to yield 6.82 g (99%) of the title compound as a light brown foam. MS (ESI): m/z=531.15 [M+NH4]+.

Workup

  1. waitat 22° C. for 22 hr
  2. concentrationthe mixture was concentrated in vacuo
  3. customto afford a gum
  4. washThis gum was washed with methanol
  5. customdried in vacuo

Sources & evidence

ORD record
ord-c68e94f45c5644c993b29b1f51ee7851
Source dataset
uspto-grants-2012_04
Patent number
US08163793B2

Reaction notes

Loading…