Hydrochloric Acid → 3-(3-Fluoro-phenyl)-3-{2-oxo-1-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propyl]-pyrrolidin-3-yl}-propionic acid ethyl ester

HRID 2289166Notes

Reaction equation

HRID 2289166 reaction equation
Cl.Cl.[N:3]1[C:12]2[NH:11][CH2:10][CH2:9][CH2:8][C:7]=2[CH:6]=[CH:5][C:4]=1[CH2:13][CH2:14][CH2:15][NH2:16].CO[C:19](=[O:36])[CH:20]([CH2:33][CH:34]=O)[CH:21]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1)[CH2:22][C:23]([OH:25])=[O:24].Cl.[CH2:38](OCC)[CH3:39].C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[CH2:38]([O:25][C:23](=[O:24])[CH2:22][CH:21]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=1)[CH:20]1[CH2:33][CH2:34][N:16]([CH2:15][CH2:14][CH2:13][C:4]2[CH:5]=[CH:6][C:7]3[CH2:8][CH2:9][CH2:10][NH:11][C:12]=3[N:3]=2)[C:19]1=[O:36])[CH3:39]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 226782113-(5,6,7,8-Tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine dihydrochlorideHCID 541186013-(3-Fluoro-phenyl)-2-(2-oxoethyl)-pentanedioic acid 1-methyl ester

Product 1

HCID 154800273-(3-Fluoro-phenyl)-3-{2-oxo-1-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propyl]-pyrrolidin-3-yl}-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a mixture of 3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propylamine (1-8) (67 mg, 0.36 mmol) and 3-(3-fluoro-phenyl)-2-(2-oxoethyl)-pentanedioic acid 1-methyl ester 2-6A (110 mg, 0.36 mmol) in 5 mL 1,2-dichloroethane was added anhydrous hydrogen chloride in ethyl ether (1.0 M, 0.70 ml, 0.7 mmol). After 10 min, triethylamine (0.14 mL, 1.1 mmol) and 4 Å molecular sieves were added. The mixture was stirred for 3 hr. It was treated with NaBH(OAc)3 (111 mg, 0.53 mmol) and stirred for 12 hr. The reaction was quenched with 10% NaHCO3 and extracted with EtOAc (×3). The combined organic layers were washed with brine and dried (Na2SO4). After solvent removal the residue was purified by flash silica chromatography (CHCl3 /MeOH, 10:1) to provide the enantiomeric pair 2-7A as an oil.

Workup

  1. stirringstirred for 12 hr
  2. customThe reaction was quenched with 10% NaHCO3
  3. extractionextracted with EtOAc (×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customAfter solvent removal the residue
  7. customwas purified by flash silica chromatography (CHCl3 /MeOH, 10:1)

Sources & evidence

ORD record
ord-8fc1345f03da4095a646562b2ed17811
Source dataset
uspto-grants-2000_07
Patent number
US06090944

Reaction notes

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