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

HRID 1158343Notes

Reaction equation

HRID 1158343 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([CH2:13][N:14]([CH3:24])[C:15](=[O:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:10]([CH2:25][N:26]([CH:43]([CH3:45])[CH3:44])[C:27](=[O:42])[C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[CH:29]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH3:24])[C:15](=[O:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:10]([CH2:25][N:26]([CH:43]([CH3:45])[CH3:44])[C:27](=[O:42])[C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[CH:29]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

3

Reactant 1

HCID 68616928(3S,4S)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylacetyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59512485(3R,4R)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylacetyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Racemic (3R*,4R*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylacetyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester is separated into the single enantiomers by preparative chiral HPLC on a Chiralpak AD-H column (4.6×250 mm, 5 μM particle size; flow rate 1 mL/min, UV=210 nM, injection=1.7 g in 5 mL ethanol and using ethanol as the eluent to give the enantiomerically pure title compound: tR (HPLC, Chiralpak AD-H, HPLC 250×4.6 mm, ethanol, flow: 0.5 ml/min): 26.46 min; and (3S,4S)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylacetyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester: tR (HPLC, Chiralpak AD-H, HPLC 250×4.6 mm, ethanol, flow: 0.5 ml/min): 13.53 min.

Workup

  1. customRacemic (3R*,4R*)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-[(methyl-phenylacetyl-amino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester is separated into the single enantiomers by preparative chiral HPLC on a Chiralpak AD-H column (4.6×250 mm, 5 μM particle size
  2. customto give the enantiomerically pure title compound
  3. custom26.46 min
  4. custom13.53 min.

Sources & evidence

ORD record
ord-b9fc6f99bb294a2a8a5f9e4f3c0e9b2b
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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