Methyl (S)-2-(Boc-amino)-5-oxo-7-(trimethylsilyl)-6-heptynoate → (2S,5S) 2-tert-Butoxycarbonylamino-5-hydroxy-7-trimethylsilanyl-hept-6-ynoic acid methyl ester

HRID 1774476Notes

Reaction equation

HRID 1774476 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][CH2:15][C:16](=[O:23])[C:17]#[C:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)(C)C>[CH3:13][O:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:14][CH2:15][C@H:16]([OH:23])[C:17]#[C:18][Si:19]([CH3:22])([CH3:20])[CH3:21]

Participants

3

Reactant 1

HCID 86618966Methyl (S)-2-(Boc-amino)-5-oxo-7-(trimethylsilyl)-6-heptynoate

Product 1

HCID 86618967(2S,5S) 2-tert-Butoxycarbonylamino-5-hydroxy-7-trimethylsilanyl-hept-6-ynoic acid methyl esterYield 92.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A 50-L flask was charged with the product from Example 1 (2.4.3 kg, 7.11 mol) and isopropanol (29 L). The solution was sparged with dry argon gas for about 50 minutes and the reaction was run under an argon atmosphere. [(1S,2S)—N-(p-toluenesulfonyl)-1,2-diphenylethanediamine](p-cymene) ruthenium (I) (Kanto Chemical Co. Inc. Catalog #41067-95, CAS#188444-42-0, 21.31 g, 0.036 mol) was added under positive argon. The reaction was followed by HPLC and additional charges of catalyst were made (21.31 g, 0.036 mol at 6 hours and 8.27 g, 0.014 mol at 8 hours) and the mixture was stirred at room temperature overnight. After a total of 22 hours, the reaction was complete. The reaction was concentrated and isopropyl acetate was added and the concentration was continued to completely replace the alcohol solvent. The final solution was distilled to about 9 L. Heptane (20 L) was added and the mixture was stirred at room temperature for 30 minutes and at 0° C. for 1 hour. The solid was collected by filtration and the solid was washed with cold heptane (2×4 L) and dried in a vacuum oven at 35-40° C. The procedure gave 2.27 kg (91.5% yield) of white solid. 1H NMR (400 MHz, CDCl3) δ ppm 0.16 (s, 9H) 1.44 (s, 9H) 1.66-1.86 (m, 3H) 1.93-2.06 (m, 1H) 2.18 (d, J=4.67 Hz, 1H) 3.73 (s, 3H) 4.29-4.43 (m, 2H) 5.11 (d, J=7.41 Hz, 1H) 13C NMR (101 MHz, CDCl3) δ ppm 0.24, 28.56, 28.62, 33.42, 52.46, 53.14, 62.14, 79.97, 89.84, 105.77, 116.39, 154.97, 172.55.

Workup

  1. customThe solution was sparged with dry argon gas for about 50 minutes
  2. custom(21.31 g, 0.036 mol at 6 hours and 8.27 g, 0.014 mol at 8 hours)
  3. customAfter a total of 22 hours
  4. concentrationThe reaction was concentrated
  5. additionisopropyl acetate was added
  6. concentrationthe concentration
  7. distillationThe final solution was distilled to about 9 L
  8. additionHeptane (20 L) was added
  9. stirringthe mixture was stirred at room temperature for 30 minutes and at 0° C. for 1 hour
  10. filtrationThe solid was collected by filtration
  11. washthe solid was washed with cold heptane (2×4 L)
  12. customdried in a vacuum oven at 35-40° C

Sources & evidence

ORD record
ord-9e79f91ce58b4f14a0de0173da8b311e
Source dataset
uspto-grants-2016_02
Patent number
US09260411B2

Reaction notes

Loading…