Ammonium Chloride → HCID 131733991, compound

HRID 712804Notes

Reaction equation

HRID 712804 reaction equation
[Si:1]([O:18][CH2:19][C@H:20]1[CH2:24][CH2:23][C:22](=[O:25])[N:21]1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.I[CH2:44][Sn:45]([CH3:48])([CH3:47])[CH3:46].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[Si:1]([O:18][CH2:19][C@@H:20]1[N:21]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:22](=[O:25])[CH:23]([CH2:44][Sn:45]([CH3:48])([CH3:47])[CH3:46])[CH2:24]1)([C:14]([CH3:15])([CH3:16])[CH3:17])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 11044939Stannane, (iodomethyl)trimethyl-HCID 11826537HCID 11826537, compound

Product 1

HCID 131733991HCID 131733991, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-tert-butyl 2-(((tert-butyldiphenylsilyl)oxy)methyl)-5-oxopyrrolidine-1-carboxylate (D29) (6 g, 13.23 mmol) in THF (80 ml) cooled at −70° C., LiHMDS 1M solution in THF (17.2 ml) was added dropwise over a period of minutes. The reaction was kept at −78° C. for 1 h before adding (iodomethyl)trimethylstannane (6.04 g, 19.84 mmol) over a period of 5 minutes. The mixture was allowed to warm at −35 and stirred at this temperature for 2 hrs. NH4Cl sat. sol (15 ml) was added and the mixture diluted with EtOAc (40 ml). The organic layer was separated and the aqueous phase acidified to pH˜4 with 0.5N HCl and the latter re-extracted with EtOAc (3×50 ml). The organic phases were combined, dried over Na2SO4 and evaporated in vacuo. The residue was purified by Biotage SNAP-Si (50 g) eluting with a mixture cHex/EtOAc from 100/0 to 90/10. Collected fractions after solvent evaporation afforded the title compound (D30) as diastereoisomer mixture (3.2 g).

Workup

  1. temperatureto warm at −35
  2. customThe organic layer was separated
  3. extractionthe latter re-extracted with EtOAc (3×50 ml)
  4. dry with materialdried over Na2SO4
  5. customevaporated in vacuo
  6. customThe residue was purified by Biotage SNAP-Si (50 g)
  7. washeluting with a mixture cHex/EtOAc from 100/0 to 90/10
  8. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-f5bba73f54e141769ddea0e1f051634e
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

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