Aniline → (3R*,4R*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-phenylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158338Notes

Reaction equation

HRID 1158338 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH:34]=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([CH2:34][NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[CH2:12]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 6115AnilineHCID 5049666Sodium triacetoxyborohydrideHCID 59512275(3S*,4R*)-3-formyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59512285(3R*,4R*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-phenylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (3S*,4R*)-3-formyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (100 mg, 0.20 mmol) and aniline (26 μL, 0.28 mmol) in 1,2-dichloroethane (5 mL) is stirred 25 min, before the addition of NaBH(OAc)3 (60 mg, 0.28 mmol) follows. The solution is stirred overnight at RT, 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 97:3) to give the title product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.25. MS (LC-MS): 570.0 [M+H]+; tR (HPLC, nucleosil C18 column, 10-100% CH3CN/H2O/ 5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 5.31 min.

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 97:3)

Sources & evidence

ORD record
ord-d0819ece68f349c59f837e1a07d68e77
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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