Tert-Butylamine → 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate

HRID 2246597Notes

Reaction equation

HRID 2246597 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C:20](=O)[CH2:19][C@H:18]2[NH:24][C:25](=[O:33])[O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:13]1=[O:34])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:35]([NH2:39])([CH3:38])([CH3:37])[CH3:36].C([BH3-])#N.[Na+].[OH-].[Na+]>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].CO>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([C@H:17]2[CH2:22][CH2:21][C@@H:20]([NH:39][C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:19][C@H:18]2[NH:24][C:25](=[O:33])[O:26][CH2:27][CH2:28][Si:29]([CH3:30])([CH3:31])[CH3:32])[C:13]1=[O:34])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6385Tert-ButylamineHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 866181582-(trimethylsilyl)ethyl (1R,2S)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-oxocyclohexylcarbamate

Product 1

HCID 866181402-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamateYield 83%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(trimethylsilyl)ethyl (1R,2S)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-oxocyclohexylcarbamate (0.550 g, 1.123 mmol) in methylene chloride (0.4 mL) was added t-butylamine (1.180 ml, 11.23 mmol) and Titanium(IV) isopropoxide (6.63 ml, 22.47 mmol). This mixture was stirred for 2 h before sodium cyanoborohydride (127 mg, 2.022 mmol) and MeOH (1 mL) were added. After 2 h, methylene chloride (50 mL) was added, followed by 1N NaOH. The mixture was filtered through Celite to remove the titanium salts. The filtrate was dried and concentrated in vacuo to give 2-(trimethylsilyl)ethyl (1R,2S,5R)-2-((S)-3-benzyloxycarbonylamino-2-oxopyrrolidin-1-yl)-5-(tert-butylamino)cyclohexylcarbamate and its 5S diastereomer as a mixture (510 mg, 0.933 mmol, 83% yield). LC/MS found [M+H]+=547.31.

Workup

  1. additionwere added
  2. filtrationThe mixture was filtered through Celite
  3. customto remove the titanium salts
  4. customThe filtrate was dried
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7ec92587c0914631a5a0427e4cb359d3
Source dataset
uspto-grants-2010_03
Patent number
US07687508B2

Reaction notes

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