Diethyldithiophosphate → benzyl ((1S,2S)-3-amino-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-3-thioxopropyl)carbamate

HRID 1028614Notes

Reaction equation

HRID 1028614 reaction equation
[Si:1]([O:8][C@H:9]([C:23]#[N:24])[C@@H:10]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([S:27]P([O-])(OCC)=S)C>O>[NH2:24][C:23](=[S:27])[C@@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[C@@H:10]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH3:11]

Participants

4

Reactant 2

HCID 53249491DiethyldithiophosphateHCID 86603431benzyl ((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate

Product 1

HCID 86603432benzyl ((1S,2S)-3-amino-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-3-thioxopropyl)carbamate

Reagents, catalysts & solvents 1

HCID 962WaterCatalyst

Procedure

A mixture of benzyl ((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate (115.6 mg, 0.287 mmol), diethyldithiophosphate (1 mL) and water (3 drops) was stirred overnight at room temperature. The reaction mixture was partitioned between saturated NaHCO3 (40 mL) and EtOAc (40 mL). The aqueous layer was separated and extracted with EtOAc (2×40 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-40% EtOAc in hexanes gradient) to afford benzyl ((1S,2S)-3-amino-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methyl-3-thioxopropyl)carbamate as a colorless oil. Rf=0.30 (20% EtOAc in hexanes). LCMS calc.=383.2; found=383.1 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 8.36 (s, 1H), 7.87 (s, 1H), 7.37-7.29 (m, 5H), 5.13 (m, 2H), 4.85 (d, J=8.2 Hz, 1H), 4.72 (s, 1H), 4.47 (m, 1H), 1.05 (d, J=6.7 Hz, 3H), 0.96 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned between saturated NaHCO3 (40 mL) and EtOAc (40 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with EtOAc (2×40 mL)
  4. dry with materialThe combined extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. customThis was purified by flash chromatography (Si, 12×160 mm, 0-40% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-dae25cf0b90f4dac95c0b7c86257f825
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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