1,2-Dichloroethane → HCID 44600522, compound

HRID 882754Notes

Reaction equation

HRID 882754 reaction equation
[C:1]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[CH:18]1([N:22]2[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:21][CH2:20][CH2:19]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C.C([O-])(O)=O.[Na+]>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([N:25]1[CH2:26][CH2:27][CH2:28][N:22]([CH:18]2[CH2:19][CH2:20][CH2:21]2)[CH2:23][CH2:24]1)=[O:12])=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 69002457HCID 69002457, compound

Product 1

HCID 44600522HCID 44600522, compoundYield 56.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of N-Boc-trans-4-hydroxy-L-proline (1.0 g, 4.32 mmol), 1-cyclobutyl-[1,4]diazepane hydrochloride (981 mg, 4.32 mmol), EDC (869 mg, 4.54 mmol) and HOBt (583 mg, 4.32 mmol) in DMF (22 mL) was added Et3N (1.2 mL, 8.64 mmol). The solution was allowed to stir overnight at room temperature (rt). The mixture was diluted with 5% aqueous (aq.) NaHCO3 and extracted with CH2Cl2 (3×). The combined organic layers were dried and concentrated. Purification by FCC provided the desired product (897 mg, 56%). MS (ESI): mass calcd. for C19H33N3O4, 367.25; m/z found, 368.6 [M+H]+. 1H NMR (CDCl3): 4.81-4.67 (m, 1H), 4.59-4.48 (m, 1H), 3.79-3.42 (m, 6H), 2.92-2.80 (m, 1H), 2.63-2.30 (m, 4H), 2.26-2.07 (m, 2H), 2.07-1.97 (m, 3H), 1.91-1.75 (m, 4H), 1.73-1.54 (m, 2H), 1.48-1.39 (m, 9H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. customThe combined organic layers were dried
  3. concentrationconcentrated
  4. customPurification by FCC

Sources & evidence

ORD record
ord-de35d3d59a19417e8baad5682117db88
Source dataset
uspto-grants-2012_08
Patent number
US08236792B2

Reaction notes

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