Dimethylformamide → HCID 23520173, compound

HRID 1008275Notes

Reaction equation

HRID 1008275 reaction equation
[C:1](Cl)(=[O:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].Br[CH2:10][C:11]([O:13][C:14]([CH3:17])(C)C)=[O:12].[CH2:18]([O:25]C(=O)[C@@H]1CCCN1)C1C=CC=CC=1.[CH3:33][CH2:34]N(C(C)C)C(C)C.[CH3:42]CN=C=NCCCN(C)C.C1CN([P+](ON2N=NC3[CH:73]=[CH:74][CH:75]=[CH:76][C:71]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CC(C)N=C=NC(C)C.[CH3:95][N:96]([CH:98]=[O:99])C>C(OCC)(=O)C>[CH3:18][O:25][C:1](=[O:7])[CH2:2][C@@H:3]([CH2:4][CH2:5][CH2:6][CH3:42])[C:98]([N:96]1[CH2:95][CH2:34][CH2:33][C@H:10]1[C:11]([O:13][CH2:14][C:17]1[CH:73]=[CH:74][CH:75]=[CH:76][CH:71]=1)=[O:12])=[O:99]

Participants

10

Reactant 8

HCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 67340Hexanoyl chlorideHCID 79177tert-Butyl bromoacetateHCID 81531DiisopropylethylamineHCID 736155Benzyl L-prolinateHCID 2724699PyBOP

Product 1

HCID 23520173HCID 23520173, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of mono-4-methyl 2-(R)-butylsuccinic acid, (prepared in three steps from hexanoylchloride and t-butyl bromoacetate as described below; 1 mmol) in DMF was added proline O-benzyl ester (1 mmol), DIEA (0.4 mL, 2.3 mmol), and a coupling reagent (e.g. EDCI, PyBOP, DIC, etc.; 1 mmol). The mixture was stirred overnight, then diluted with ethyl acetate and washed with aqueous HCl (1 N), water, saturated sodium bicarbonate, brine, and then dried (Na2SO4). The filtrate was concentrated and then purified on silica gel (Merck 60; ethyl acetate/hexane) to afford methyl-3-(R)-butyl-3-(2-(S)-benzyloxycarbonylpyrrolidin-1-ylcarbonyl)propionate. To this amide (0.1 mmol) in ethylacetate (10 mL) was added 10% Pd/C (100 mg) and the solution stirred under a hydrogen atmosphere for 8 h. The suspension was filtered through a Celite plug and then concentrated to afford methyl-3-(R)-butyl-3-(2-(S)-carboxypyrrolidin-1-ylcarbonyl)propionate E-2.

Workup

  1. washwashed with aqueous HCl (1 N), water, saturated sodium bicarbonate, brine
  2. dry with materialdried (Na2SO4)
  3. concentrationThe filtrate was concentrated
  4. custompurified on silica gel (Merck 60; ethyl acetate/hexane)

Sources & evidence

ORD record
ord-270bf75eecdd4e44b053eae428519a92
Source dataset
uspto-grants-2004_09
Patent number
US06797820B2

Reaction notes

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