Ethylmorpholine → tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-(benzyloxycarbonyl)propyl]amino}carbonyl)-6-(3'-methoxy-2-methylbiphen-4-yl)hex-5-enoate

HRID 1700996Notes

Reaction equation

HRID 1700996 reaction equation
[CH3:1][C:2]([CH3:30])([CH3:29])[C@H:3]([NH:14][C:15]([C@H:17]([CH2:26][CH:27]=[CH2:28])[CH2:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:16])[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].I[C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=2)=[C:34]([CH3:46])[CH:33]=1.C(N1CCOCC1)C>C(#N)C>[CH3:1][C:2]([CH3:30])([CH3:29])[C@H:3]([NH:14][C:15]([C@H:17]([CH2:26]/[CH:27]=[CH:28]/[C:32]1[CH:33]=[C:34]([CH3:46])[C:35]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=2)=[CH:36][CH:37]=1)[CH2:18][C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])=[O:16])[C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:5]

Participants

5

Reactant 3

HCID 7525EthylmorpholineHCID 183192524-Iodo-1-(3-methoxyphenyl)-2-methylbenzeneHCID 57079181HCID 57079181, compound

Product 1

HCID 59875766tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-(benzyloxycarbonyl)propyl]amino}carbonyl)-6-(3'-methoxy-2-methylbiphen-4-yl)hex-5-enoateYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

By the method of Preparation 3 a), tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-(benzyloxycarbonyl)propyl]amino}carbonyl)hex-5-enoate (2.085 g, 5.0 mmol) was reacted with 4-iodo-1-(3-methoxyphenyl)-2-methylbenzene (Preparation 20) (889 mg, 2.13 mmol) under palladium catalysis, using N-ethylmorpholine as base at reflux in acetonitrile for 14.5 h. Work-up as before followed by purification by flash chromatography (hexane:ethyl acetate=10:1) gave mainly tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-(benzyloxycarbonyl)propyl]amino}carbonyl)-6-(3′-methoxy-2-methylbiphen-4-yl)hex-5-enoate as a pale yellow gum (1.043 gm, 80%). 1H nmr suggested that two alkene isomers, the (5Z) and (4E) were also present. The mixture of alkenes was taken onto the next step (see b, below).

Workup

  1. custombefore followed by purification by flash chromatography (hexane:ethyl acetate=10:1)

Sources & evidence

ORD record
ord-22887bc6dc9344808830a0891c2f16b1
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

Loading…