4-Methylmorpholine → HCID 131713594, compound

HRID 1463024Notes

Reaction equation

HRID 1463024 reaction equation
C([O:5][C:6]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])(C)(C)C.CN1CC[O:18]CC1.ClC(O[CH2:25][CH:26]([CH3:28])[CH3:27])=O.Cl.[C:30]1([CH2:36][C@@H:37]2[CH2:41][NH:40][C@H:39]([C:42]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)=[O:43])[CH2:38]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(Cl)(Cl)Cl.C(#N)C>[CH3:25][C:26]([CH3:28])([O:18][O:5][C:6]([NH:8][C@H:9]([C:11]([N:40]1[CH2:41][C@@H:37]([CH2:36][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:38][C@H:39]1[C:42]([O:44][CH2:45][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)=[O:43])=[O:13])[CH3:10])=[O:7])[CH3:27]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 85082Tert-butoxycarbonylalanineHCID 131713595HCID 131713595, compound

Product 1

HCID 131713594HCID 131713594, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 11.7 grams of tert. butyloxycarbonyl-L-alanine in 500 ml. of acetonitrile is cooled to -20° and 6.8 ml. of N-methylmorpholine is added, followed by 8.1 ml. of isobutyl chloroformate. The reaction mixture is allowed to stir for 5 minutes at -20° and a solution of 15.4 grams of 4-(S)-(phenylmethyl)-L-proline, phenylmethyl ester, hydrochloride and 6.8 ml. of N-methylmorpholine in 500 ml. of chloroform is added. The reaction mixture is allowed to warm slowly to room temperature, with stirring. After 18 hours the solvent is evaporated under reduced pressure. The oily residue is partitioned between ethyl acetate and water. The ethyl acetate layer is then washed with 0.2 N aqueous hydrochloric acid, water and with saturated aqueous sodium bicarbonate solution. The ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure to yield the desired 1-[N-(1,1-dimethylethoxycarboxy)-L-alanyl]-4-(S)-(phenylmethyl)-L-proline, phenylmethyl ester.

Workup

  1. stirringwith stirring
  2. customAfter 18 hours the solvent is evaporated under reduced pressure
  3. customThe oily residue is partitioned between ethyl acetate and water
  4. washThe ethyl acetate layer is then washed with 0.2 N aqueous hydrochloric acid, water and with saturated aqueous sodium bicarbonate solution
  5. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2556a327425a4543949dbdb13fbbf224
Source dataset
uspto-grants-1984_07
Patent number
US04462943

Reaction notes

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