Acetic Acid → trans-1-tert-butoxycarbonyl(2S)-(tert-butyldiphenylsilyloxy)methyl-4-dimethylaminopyrrolidine

HRID 350515Notes

Reaction equation

HRID 350515 reaction equation
N[C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([CH2:14][O:15][Si:16]([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:3]1.[CH3:33]C(O)=O.C=O.[BH3-][C:40]#[N:41].[Na+]>CO>[C:10]([O:9][C:7]([N:5]1[CH2:6][C@H:2]([N:41]([CH3:40])[CH3:33])[CH2:3][C@H:4]1[CH2:14][O:15][Si:16]([C:29]([CH3:32])([CH3:31])[CH3:30])([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:8])([CH3:13])([CH3:11])[CH3:12]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69332987trans-4-amino-1-tert-butoxycarbonyl(2S)-(tert-butyldiphenylsilyloxy)methylpyrrolidine

Product 1

HCID 69334202trans-1-tert-butoxycarbonyl(2S)-(tert-butyldiphenylsilyloxy)methyl-4-dimethylaminopyrrolidineYield 78%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of trans-4-amino-1-tert-butoxycarbonyl-(2S)-(tert-butyldiphenylsilyloxy) methylpyrrolidine (400 mg, 0.88 mmol), AcOH (120 ml, 2.0 mmol), and 37% HCHO aq (500 ml) in MeOH (10 ml) was added NaBH3CN (111 mg, 1.76 mmol) at 0° C. The reaction mixture was stirred at room temperature for 18 hr. After concentrated in vacuo, water was added and extracted with CH2Cl2. The extract was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel with MeOH—CH2Cl2 (3:97, v/v) as eluent to give trans-1-tert-butoxycarbonyl-(2S)-(tert-butyldiphenylsilyloxy)methyl-4-dimethylaminopyrrolidine (330 mg, 78%) as a pale yellow oil. 1H-NMR (CDCl3) δ 1.06 (s, 9H), 1.33 and 1.45 (each s, total 9H), 1.80–2.25 (m, 2H), 2.23 (br s, 6H), 2.95–4.05 (m, 6H), 7.36–7.39 (m, 6H), 7.63–7.65 (m, 4H).

Workup

  1. concentrationAfter concentrated in vacuo, water
  2. additionwas added
  3. extractionextracted with CH2Cl2
  4. dry with materialThe extract was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography on silica gel with MeOH—CH2Cl2 (3:97

Sources & evidence

ORD record
ord-f2c222e6c91e4c5db2fab72f5f5dbebe
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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