1,2-Dichloroethane → Boc-D-cyclohexylglycine proline methyl ester

HRID 482554Notes

Reaction equation

HRID 482554 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@@H:9]([C:16]([OH:18])=[O:17])[CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])[CH3:3].Cl.[CH3:20][O:21][C:22](=[O:28])[C@@H:23]1[CH2:27][CH2:26][CH2:25][NH:24]1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>CN(C=O)C.O>[CH3:4][C:2]([O:5][C:6]([NH:8][C@@H:9]([C:16]([OH:18])=[O:17])[CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)=[O:7])([CH3:1])[CH3:3].[CH3:20][O:21][C:22](=[O:28])[C@@H:23]1[CH2:27][CH2:26][CH2:25][NH:24]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 2733200methyl L-prolinate hydrochlorideHCID 7014890(2R)-2-(((tert-butoxy)carbonyl)amino)-2-cyclohexylacetic acid

Product 1

HCID 131720805Boc-D-cyclohexylglycine proline methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 8.0 g (31.0 mmol)of Boc-D-cyclohexylglycine and 5.8 g (35 mmol) of proline methyl ester HCl salt in 100 ml of anh. DMF, mixed with 5.8 g (37.2 mmol) of HOBt with the pH adjusted to 7-8 with N-methylmorpholine (to moistened narrow-range pH paper), was treated with 7.9 g (40.3 mmol) of EDC and stirred for 18 hr in a nitrogen atmosphere. After 20 hr water (10 ml) was added, the solution concentrated in vacuo and partitioned with 400 ml EtOAc and 200 ml H2O, washing with dil. NaHCO3, H2O, dil. KHSO4, and twice with 50% satd NaCl, dried over Na2SO4 and concentrated under reduced pressure to give an oil. This crude material was chromatographed on 300 g silica gel in 1:1 (v/v) EtOAc/hexane to afford, after pooling of fractions, intermediary 26-1.

Workup

  1. concentrationthe solution concentrated in vacuo
  2. custompartitioned with 400 ml EtOAc and 200 ml H2O
  3. washwashing with dil. NaHCO3, H2O, dil. KHSO4
  4. dry with materialtwice with 50% satd NaCl, dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto give an oil
  7. customThis crude material was chromatographed on 300 g silica gel in 1:1 (v/v) EtOAc/hexane
  8. customto afford

Sources & evidence

ORD record
ord-5a569b9e33a843c89b30e1b744d43e9c
Source dataset
uspto-grants-1998_08
Patent number
US05798377

Reaction notes

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