tert-Butyldimethylsilyl chloride → (+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl ester

HRID 501644Notes

Reaction equation

HRID 501644 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C@@H:4]1[C@H:9]([OH:10])[CH2:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].CCN(C(C)C)C(C)C.[Si:28](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3](=[O:18])[C@@H:4]1[C@H:9]([O:10][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12]

Participants

6

Reactant 3

HCID 28928tert-Butyldimethylsilyl chloride2×HCID 81531Diisopropylethylamine2×HCID 59754228rac-1-tert-butyl 2-methyl (2R,3S)-3-hydroxypiperidine-1,2-dicarboxylate

Product 1

HCID 68458695(+/-)-(2S,3R)-1-tert-Butoxycarbonyl-3-(tert-butyldimethylsilanyloxy)pipecolic acid methyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 77C (3.3 g, 12.7 mmol) in DCM (50 mL) was added DIPEA (6.63 mL, 38.1 mmol), tert-butyldimethylsilyl chloride (3.83 g, 25.4 mmol, 2.0 equiv) and DMAP (310 mg, 5.24 mmol, 0.2 equiv). The resulting mixture was stirred at rt overnight. TLC showed no completion and therefore another 2.2 mL of DIPEA and 1.91 g of tert-butyldimethylsilyl chloride were added and stirred at rt for 3 days. The mixture was concentrated and the residue was diluted with EtOAc (100 mL), washed with 0.5 N HCl (2×30 mL), brine (2×30 mL), dried (MgSO4) and evaporated to give the crude product as a light pink oil. Purification of the crude product by flash chromatography (5-10% EtOAc/hexane) gave the desired product 77D (3.8 g, 81%): Rf (10% EtOAc/hexane) 0.25; HPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 4.3 min (100%); MS (ES) m/z 374 [M+1]+.

Workup

  1. stirringstirred at rt for 3 days
  2. concentrationThe mixture was concentrated
  3. additionthe residue was diluted with EtOAc (100 mL)
  4. washwashed with 0.5 N HCl (2×30 mL), brine (2×30 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customto give the crude product as a light pink oil
  8. customPurification of the crude product by flash chromatography (5-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-784f3971174b4cb0a2f23fbac050c4d8
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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