tert-Butyldimethylsilyl chloride → HCID 18761619, compound

HRID 2062037Notes

Reaction equation

HRID 2062037 reaction equation
[N:1]1([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:9][C@H:7]([OH:8])[CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].C1CCN2C(=NCCC2)CC1.[Si:31](Cl)([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32]>CN(C=O)C>[CH2:13]([O:12][C:10]([N:1]1[CH2:9][CH:7]([O:8][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:6][CH:2]1[C:3]([OH:5])=[O:4])=[O:11])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 28928tert-Butyldimethylsilyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 3915171-(Phenylmethyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate

Product 1

HCID 18761619HCID 18761619, compoundYield 140.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of Z-Hyp-OH (1, 300 g, 1.13 mol), TEA (395 mL, 2.83 mol), and DBU (17.2 g, 1.13 mol) in DMF (1.25 L) was stirred in a cold water bath while a suspension of TBS-Cl (188 g, 1.24 mol) in DMF (270 mL) was added slowly at 21-26° C. [Note: moderately exothermic]. The resulting thin suspension was stirred for 22 h at ambient temperature. The reaction mixture was cooled to 2° C. and quenched with water (1.54 L) at 26° C. [Note: the pH of the aqueous layer was 8.5-9.0]. MTBE (3 L) was added and the mixture was acidified to pH 3-4 with conc. HCl (168 g) at 17-19° C. The organic layer was separated and washed with water (2×1.5 L). The organic layer was concentrated in vacuo and dried by additional MTBE distillation. Toluene (2×500 mL) was added and distilled to remove moisture to provide 603 g of 2 as a light yellow-colored oil [Note: the water content by KF analysis was 508 ppm]. Based on drying a small sample of 2 to a solid, the contained weight of 2 was 412 g (96% yield, not corrected for purity). 1H NMR (300 MHz, CDCl3): δ7.34 (m, 3H), 7.29 (m, 2H), 5.24-5.11 (m, 2H), 4.52 (m, 1H), 4.43 (m, 1H), 3.64-3.42 (m, 2H), 2.27-2.09 (m, 2H), 0.85 (s, 9H), 0.06 (s, 3H), 0.04 (s, 3H) ppm; 13C NMR (75 MHz, d6-DMSO), mixture of rotomers: δ178.7, 178.4, 159.3, 158.9, 141.9, 141.8, 133.4, 133.3, 132.8, 132.6, 132.3, 131.9, 75.3, 74.6, 71.0, 71.0, 62.8, 62.3, 60.1, 59.7, 44.4, 43.4, 30.6, 30.6, 22.6, 22.6, 0.1, 0.0 ppm. Mass spectrum (ESI), m/z 379.5 [(M)+; calcd for C19H29NO5Si: 379.5].

Workup

  1. additionwas added slowly at 21-26° C. [Note
  2. temperatureThe reaction mixture was cooled to 2° C.
  3. customquenched with water (1.54 L) at 26° C. [Note
  4. additionMTBE (3 L) was added
  5. customwas acidified to pH 3-4 with conc. HCl (168 g) at 17-19° C
  6. customThe organic layer was separated
  7. washwashed with water (2×1.5 L)
  8. concentrationThe organic layer was concentrated in vacuo
  9. dry with materialdried by additional MTBE distillation
  10. additionToluene (2×500 mL) was added
  11. distillationdistilled
  12. customto remove moisture

Sources & evidence

ORD record
ord-8be1db7e19014600b9430a59dd8d55f8
Source dataset
uspto-grants-2012_10
Patent number
US08283372B2

Reaction notes

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