Methanol → Benzyl (s)-1-((1s,2r,4r/s)-4-(tert-butylamino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

HRID 1455392Notes

Reaction equation

HRID 1455392 reaction equation
[O:1]=[C:2]1[C@@H:6]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:5][CH2:4][N:3]1[C@H:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][C@H:19]1[CH2:25][CH2:26][CH3:27].[C:28]([NH2:32])([CH3:31])([CH3:30])[CH3:29].CO.[BH4-].[Na+]>C(Cl)Cl.[OH-].[Na+].CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[C:28]([NH:32][CH:21]1[CH2:22][CH2:23][C@H:18]([N:3]2[CH2:4][CH2:5][C@H:6]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:2]2=[O:1])[C@H:19]([CH2:25][CH2:26][CH3:27])[CH2:20]1)([CH3:31])([CH3:30])[CH3:29]

Participants

8

Reactant 4

HCID 887MethanolHCID 6385Tert-ButylamineHCID 4311764Sodium borohydrideHCID 86596864benzyl (S)-2-oxo-1-((1S,2R)-4-oxo-2-propylcyclohexyl)pyrrolidin-3-ylcarbamate

Product 1

HCID 90985767Benzyl (s)-1-((1s,2r,4r/s)-4-(tert-butylamino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-ylcarbamate

Reagents, catalysts & solvents 3

HCID 178460666HCID 178460666, compoundCatalystHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

Examples 2t and 2u, Step 6: A sample of benzyl (S)-2-oxo-1-((1S,2R)-4-oxo-2-propylcyclohexyl)pyrrolidin-3-ylcarbamate (114 mg) was dissolved in Ti(OiPr)4 (1.5 mL, 5.0 mmol) and tert-butylamine (0.14 mL, 1.8 mmol). The resultant solution was stirred at RT for 3 h before being cooled to 0° C. and charged successively with MeOH (2 mL) and NaBH4 (22.8 mg, 0.6 mmol). The mixture was stirred for 90 min while the solution slowly warmed to RT. The solution was diluted with methylene chloride (10 mL) and 0.5 N NaOH was added. The resultant suspension was filtered through a pad of Celite with EtOAc washings and the filtrate was dried, filtered, and concentrated in vacuo to afford benzyl (S)-1-((1S,2R,4R/S)-4-(tert-butylamino)-2-propylcyclohexyl)-2-oxopyrrolidin-3-ylcarbamate as an inseparable mixture of diastereomers. MS found: (M+H)+=430.5.

Workup

  1. temperatureslowly warmed to RT
  2. additionwas added
  3. filtrationThe resultant suspension was filtered through a pad of Celite with EtOAc washings
  4. customthe filtrate was dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a47c3e8c0d8d4b91a6a3b9f650dcd4a4
Source dataset
uspto-grants-2009_01
Patent number
US07482335B2

Reaction notes

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