4-Methylmorpholine → L-isoleucine, N-[1-(2-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-2-oxoethyl)-L-Prolyl] benzylamide

HRID 2293395Notes

Reaction equation

HRID 2293395 reaction equation
[C:1]([CH2:4][N:5]1[CH2:27][CH2:26][CH2:25][C@H:6]1[C:7]([N:9]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:10](=[O:17])[C@H:11]([C@H:13]([CH2:15][CH3:16])[CH3:14])[NH2:12])=[O:8])(O)=[O:2].CN1CCOCC1.ClC(OCC(C)C)=O.[O:43]1[C:47]2([CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[O:46][CH2:45][CH2:44]1>C(#N)C>[O:43]1[C:47]2([CH2:52][CH2:51][N:50]([C:1](=[O:2])[CH2:4][N:5]3[CH2:27][CH2:26][CH2:25][C@H:6]3[C:7]([N:9]([CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:10](=[O:17])[C@H:11]([C@H:13]([CH2:15][CH3:16])[CH3:14])[NH2:12])=[O:8])[CH2:49][CH2:48]2)[O:46][CH2:45][CH2:44]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 131720284L-isoleucine, N-[1-(carboxymethyl)-L-prolyl] benzylamide

Product 1

HCID 131720285L-isoleucine, N-[1-(2-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-2-oxoethyl)-L-Prolyl] benzylamideYield 83.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A -5° C. solution of L-isoleucine, N-[1-(carboxymethyl)-L-prolyl] benzylamide (254 mg, 0.67 mmol, 1.0 eq), N-methylmorpholine (96 uL, 0.88 mmol, 1.30 eq) in acetonitrile (7 mL) was treated with isobutyl chloroformate (96 uL, 0.74 mmol, 1.1 eq) followed by 1,4-dioxa-8-aza-spiro[4.5] decane (0.193 g, 1.35 mmol, 2.0 eq). Purification by flash chromatography provided 280 mg (83%) of L-isoleucine, N-[1-(2-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-2-oxoethyl)-L-Prolyl] benzylamide as a colorless oil

Workup

  1. customPurification by flash chromatography

Sources & evidence

ORD record
ord-f71cac794704451f808645c94a590978
Source dataset
uspto-grants-1997_11
Patent number
US05686424

Reaction notes

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