Isopropylamine → (3S*,4R*)-4-(Isopropylamino-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

HRID 1158326Notes

Reaction equation

HRID 1158326 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[C@H:10]([CH:11]=O)[CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7]1)=[O:5])[CH3:2].[CH:20]([NH2:23])([CH3:22])[CH3:21].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[CH2:1]([O:3][C:4]([C@H:6]1[C@H:10]([CH2:11][NH:23][CH:20]([CH3:22])[CH3:21])[CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 6363IsopropylamineHCID 5049666Sodium triacetoxyborohydrideHCID 86622385(3S*,4S*)-4-Formyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

Product 1

HCID 68617367(3S*,4R*)-4-(Isopropylamino-methyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (3S*,4S*)-4-formyl-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (2.87 g, 10.56 mmol) and isopropylamine (2.72 mL, 31.68 mmol) in 1,2-dichloroethane (150 mL) is stirred 25 min, before addition of NaBH(OAc)3 (3.12 g, 14.78 mmol) follows. The solution is stirred for 4 h, then diluted with CH2Cl2 and washed with an aqueous saturated solution of NaHCO3. The combined organic extracts are dried over Na2SO4 and concentrated. The crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 80:20) to give the title product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.1.

Workup

  1. washwashed with an aqueous saturated solution of NaHCO3
  2. dry with materialThe combined organic extracts are dried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 80:20)

Sources & evidence

ORD record
ord-2ead65728d75424a83f49ac7c093ee9b
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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