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

HRID 1700991Notes

Reaction equation

HRID 1700991 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].[CH3:31][C:32]1[CH:33]=[C:34](Br)[CH:35]=[CH:36][C:37]=1[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=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:34]1[CH:35]=[CH:36][C:37]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[C:32]([CH3:31])[CH:33]=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 99648454-Bromo-2-methylbiphenylHCID 57079181HCID 57079181, compound

Product 1

HCID 59875769tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-(benzyloxycarbonyl)propyl]amino}carbonyl)-6-[3-methyl-(4-phenyl)phenyl]hex-5-enoateYield 75.5%

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 3-methyl-4-phenylbromobenzene (1.855 g, 7.5 mmol) under palladium catalysis, using N-ethylmorpholine as base at reflux in acetonitrile for 16.5 h. Work-up as before followed by purification by repeated flash chromatography (first column hexane:ether=4:1; second column toluene:ether=20:1) gave mainly tert-butyl (3R,5E)-3-({[(1S)-2,2-dimethyl-1-(benzyloxycarbonyl)propyl]amino}carbonyl)-6-[3-methyl-(4-phenyl)phenyl]hex-5-enoate as a pale yellow gum (2.205 gm, 75%). 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 c, below). δH (400 MHz, CDCl3) 0.95 (9H, s), 1.42 (9H, s), 2.26 (3H, s), 2.35 (1H, m), 2.45 (1H, dd, 3 and 17 Hz), 2.54 (1H, dt, J=15 and 6.5),2.69 (1H, dd, J=9 and 17 Hz), 2.77 (1H, m), 4.52 (1H, d, J=10 Hz), 4.97 (1H, d, J=12 Hz), 5.06 (1H, d, J=12 Hz), 6.16 (1H, dt, J=18 and 7 Hz), 6.42 (2H, m), 7.29 (13H, complex).

Workup

  1. custombefore followed by purification by repeated flash chromatography (first column hexane:ether=4:1; second column toluene:ether=20:1)

Sources & evidence

ORD record
ord-461ef38db3eb4b6da0963c67d6fa884a
Source dataset
uspto-grants-2002_02
Patent number
US06350907B1

Reaction notes

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