18-Crown-6 → (r)-5-Biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(e)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 588317Notes

Reaction equation

HRID 588317 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.[K+].C1O[CH2:51][CH2:50]OCCOCCOCCOCCOC1.CC(O[CH:58](N(C)C)[N:59](C)C)(C)C.[CH3:65]N(C(N(C)C)N(C)C)C.C(OC(O[C:85]([CH3:88])([CH3:87])C)N(C)C)(C)(C)C>>[C:1]([O:5][C:6]([N:8]1[C@H:9]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[CH:19][CH:20]=2)[CH2:10]/[C:11](=[CH:58]\[N:59]([CH:50]([CH3:51])[CH3:65])[CH:85]([CH3:87])[CH3:88])/[C:12]1=[O:13])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 6

HCID 2855718-Crown-6HCID 79831N,N,N',N',N'',N''-HexamethylmethanetriamineHCID 79885tert-Butoxy bis(dimethylamino)methane2×HCID 5477121,1-bis(1,1-dimethylethoxy)-N,N,N-trimethylamineHCID 23688904Potassium hexafluorophosphateHCID 46193436(S)-2-biphenyl-4-ylmethyl-5-oxopyrrolidine-1-carboxylic acid t-butyl ester

Product 1

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

Procedure

(S)-2-Biphenyl-4-ylmethyl-5-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (8-a, R1=Boc) (2 mmol) is added to potassium hexafluorophosphate (1 eq) and 18-crown-6 (1 eq). Bredereck's reagent [Tris(dimethylamino)methane (13, R6=Me, R7=Me), Tert-Butoxy-bis(dimethylamino)methane (14, R6=Me, R7=Me, R8=tBu) and N,N-Dimethylformamide di-tert-butyl acetal (15, R6=Me, R7=Me, R8=tBu)] (4 ml) is added. The mixture is then stirred at ambient temperature for 3 h to afford (R)-5-biphenyl-4-ylmethyl-3-[1-dimethylaminometh-(E/Z)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (7-a, R1=Boc, R6=Me, R7=Me) or a salt thereof. The solutions are analysed by TLC (50% ethyl acetate in hexane). RF 0.21 (salt of 7-a, R1=Boc, R6=Me, R7=Me); RF 0.27 (7-a, R1=Boc, R6=Me, R7=Me); RF 0.68 (8-a, R1=Boc).

Sources & evidence

ORD record
ord-3a395fe4c13a4c67b7d574e24515cd9c
Source dataset
uspto-grants-2016_01
Patent number
US09227934B2

Reaction notes

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