Dichloromethane → (trans)-1-[[(3-Ethoxy-3-oxopropyl)ethylamino]carbonyl]-4-hydroxy-L-proline, phenylmethyl ester

HRID 485330Notes

Reaction equation

HRID 485330 reaction equation
ClCCl.Cl.[OH:5][C@H:6]1[CH2:10][NH:9][C@H:8]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[CH2:7]1.[CH3:21][N:22]1[CH2:27][CH2:26]O[CH2:24][CH2:23]1.OC1CN[C@H]([C:34]([O:36][CH2:37][C:38]2C=CC=CC=2)=[O:35])C1.C(OCC)(=[O:46])C>>[CH2:37]([O:36][C:34](=[O:35])[CH2:26][CH2:27][N:22]([CH2:23][CH3:24])[C:21]([N:9]1[CH2:10][C@H:6]([OH:5])[CH2:7][C@H:8]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:46])[CH3:38]

Participants

6

Reactant 5

HCID 6344Dichloromethane2×HCID 79724-MethylmorpholineHCID 8857Ethyl AcetateHCID 139375174-hydroxy-L-proline, phenylmethyl esterHCID 16212860Benzyl (4R)-4-hydroxy-L-prolinate--hydrogen chloride (1/1)

Product 1

HCID 131714305(trans)-1-[[(3-Ethoxy-3-oxopropyl)ethylamino]carbonyl]-4-hydroxy-L-proline, phenylmethyl ester

Procedure

This residue is dissolved in 30 ml. of dichloromethane and (trans)-4-hydroxy-L-proline, phenylmethyl ester, hydrochloride (6.9 g., 1.2 eq.) is added. To the resulting suspension is added dropwise N-methylmorpholine (5.6 ml., 2.4 eq.) in 20 ml. of dichloromethane. The resulting mixture is stirred at room temperature for 15 hours. The solvent is removed at reduced pressure and the residue taken up in ethyl acetate. This is washed with water (twice), 1N hydrochloric acid (twice), 1N sodium bicarbonate (twice), and once with brine. After drying (MgSO4), the solvent is removed at reduced pressure. The residue is flash chromatographed (Whatman silica gel LPS-1, hexane:ethyl acetate; 65:35) to give 7.72 g. of (trans)-1-[[3-ethoxy-3-oxopropyl)ethylamino]carbonyl]-4-hydroxy-L-proline, phenylmethyl ester as a colorless oil; TLC (silica gel, ethyl acetate) Rf =0.34.

Workup

  1. dissolutionThis residue is dissolved in 30 ml
  2. customThe solvent is removed at reduced pressure
  3. washThis is washed with water (twice), 1N hydrochloric acid (twice), 1N sodium bicarbonate (twice), and once with brine
  4. dry with materialAfter drying (MgSO4)
  5. customthe solvent is removed at reduced pressure
  6. customchromatographed (Whatman silica gel LPS-1, hexane:ethyl acetate; 65:35)
  7. customto give 7.72 g

Sources & evidence

ORD record
ord-207a0729442548fcb09265955604ecc1
Source dataset
uspto-grants-1985_08
Patent number
US04536501

Reaction notes

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