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

HRID 1068102Notes

Reaction equation

HRID 1068102 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].C(N(CC)C(C)C)(C)C.[Si:25](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([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:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[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 Step A) in 12.0 mL of CH2Cl2 at 0° C. was treated with 0.99 mL (5.7 mmol) of N,N-diisopropylethylamine and 855 mg (5.6 mmol) of t-butyldimethylsilyl 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); 1HNMR (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-179bd09c22cd4bfcb1d336c5a1692012
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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