tert-Butyldimethylsilyl chloride → 1-(Prop-2-enyl)-3-(r)-(t-butyldimethylsilyloxymethyl)-4-(s)-(3-thienyl)pyrrolidine

HRID 1386734Notes

Reaction equation

HRID 1386734 reaction equation
[CH2:1]([N:4]1[CH2:8][C@H:7]([C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)[C@@H:6]([CH2:14][OH:15])[CH2:5]1)[CH:2]=[CH2:3].CCN(C(C)C)C(C)C.[C:25]([Si:29](Cl)([CH3:31])[CH3:30])([CH3:28])([CH3:27])[CH3:26]>C(Cl)Cl>[CH2:1]([N:4]1[CH2:8][C@H:7]([C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)[C@@H:6]([CH2:14][O:15][Si:29]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:31])[CH3:30])[CH2:5]1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 28928tert-Butyldimethylsilyl chlorideHCID 81531DiisopropylethylamineHCID 213410491-(Prop-2-enyl)-3-(r)-(hydroxymethyl)-4-(s)-(3-thienyl)pyrrolidine

Product 1

HCID 213410501-(Prop-2-enyl)-3-(r)-(t-butyldimethylsilyloxymethyl)-4-(s)-(3-thienyl)pyrrolidineYield 77.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1.06 g (4.75 mmol) of 1-(prop-2-enyl)(3-(R)-(hydroxymethyl))-4-(S)-(3-thienyl)pyrrolidine (from EXAMPLE 87, Step A) in 12.0 mL of CH2Cl2 at 0° C. was treated with 0.99 mL (5.7 mmol) of DIEA and 855 mg (5.6 mmol) of t-butyldimethyl silyl chloride. After warming to rt and stirring for 20 h, the solution was partitioned between 100 mL of ether and 100 mL of H2O. After separating the phases, the aqueous layer was extracted with 100 mL of ether. The combined organic phases were dried over MgSO4 and concentrated. The residue was purified by flash chromatography eluting with 3:1 v/v hexanes/EtOAc to yield 1.24 g (77%) of the title compound: RF: 0.54 (3:2 v/v hexanes/EtOAc); 1H NMR (300 MHz) δ 0.0 (s, 6H), 0.86 (s, 9H), 2.35 (m, 1H), 2.52-2.71 (m, 3H), 2.97-3.20 (m, 4H), 3.54-3.66 (m, 2H), 5.06-5.21 (m, 2H), 5.89 (m, 1H). 6.98-7.02 (m, 2H), 7.22 (m, 1H).

Workup

  1. customthe solution was partitioned between 100 mL of ether and 100 mL of H2O
  2. customAfter separating the phases
  3. extractionthe aqueous layer was extracted with 100 mL of ether
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 3:1 v/v hexanes/EtOAc

Sources & evidence

ORD record
ord-c0ffabef90314d6886f7453639b0dad5
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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