p-Toluenesulfonic acid → HCID 58160377, compound

HRID 1477451Notes

Reaction equation

HRID 1477451 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:11]/[C:10](=[CH:26]\N(C(C)C)C(C)C)/[C:9]1=[O:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:35]([SH:39])[CH2:36][CH2:37][CH3:38].[C:40]1(C)C=C[C:43]([S:46](O)(=O)=O)=[CH:42][CH:41]=1>>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:11][CH:10]([CH:26]([S:46][CH2:43][CH2:42][CH2:41][CH3:40])[S:39][CH2:35][CH2:36][CH2:37][CH3:38])[C:9]1=[O:34])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 8012ButanethiolHCID 58160400(r)-5-Biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(e)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 58160377HCID 58160377, compound

Conditions

Temperature
25 °C

Procedure

0.5 g of 5-Biphenyl-4-ylmethyl-3-[1-dimethylamino-meth-(E/Z)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (7-a, R1=Boc, R6=Me, R7=Me) are added to 5 ml of n-butane-1-thiol. After the addition of 0.2 g of p-toluenesulfonic acid the mixture is stirred for 6 days at 25° C., then heated to 60° C. for 16 hours. The mixture is then quenched by addition of 5 ml of an 8% aqueous bicarbonate solution and any remaining n-butane-1-thiol distilled off under reduced pressure at 40° C. The aqueous phase is extracted 3 times with 5 ml ethyl acetate each and the combined organic phase evaporated to dryness at 40° C. under reduced pressure. The residue is purified by column chromatography (heptane: ethyl acetate 75:25) to afford (3R/S,5S)-5-biphenyl-4-ylmethyl-3-(bis-butylsulfanyl-methyl)-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (16-a, R1=Boc, R9=nBu, R9=nBu, Y=S). Ratio of C-3 diastereomers determined as 70:30 ((3S,5S):(3R,5S) diastereomers, respectively). 1H NMR (CDCl3): Data for mixture of diastereomers: 0.86-0.96 (6H), 1.32-1.47 (4H), 1.50-1.68 (4H), 1.62 (9H), 1.94-2.30 (2H), 2.48-2.74 (4H), 2.80-2.89 (2H), 3.10-3.16 (1H), 3.55-3.59 (1H, minor stereoisomer), 4.23-4.31 (1H, minor stereoisomer), 4.30 (1H), 4.38 (1H, minor stereoisomer), 4.43-4.47 (1H), 7.27-7.30 (2H), 7.32-7.40 (1H), 7.44-7.50 (2H), 7.56-7.65 (4H).

Workup

  1. temperatureheated to 60° C. for 16 hours
  2. customThe mixture is then quenched by addition of 5 ml of an 8% aqueous bicarbonate solution
  3. distillationany remaining n-butane-1-thiol distilled off under reduced pressure at 40° C
  4. extractionThe aqueous phase is extracted 3 times with 5 ml ethyl acetate each and the combined organic phase
  5. customevaporated to dryness at 40° C. under reduced pressure
  6. customThe residue is purified by column chromatography (heptane: ethyl acetate 75:25)

Sources & evidence

ORD record
ord-b042cafdd8694ce8afe21d7a22940731
Source dataset
uspto-grants-2016_08
Patent number
US09403766B2

Reaction notes

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