Potassium Carbonate → tert-butyl (2R,5R)-2-ethynyl-5-(tert-butyldimethylsilyloxy-methyl)morpholine-4-carboxylate

HRID 629734Notes

Reaction equation

HRID 629734 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[N:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][C@@H:13]([CH:23]=O)[O:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:25]([O-])([O-])=O.[K+].[K+]>CO>[C:23]([C@H:13]1[O:12][CH2:11][C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3])[N:15]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:14]1)#[CH:25]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 86726303Tert-butyl (2S,5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-formylmorpholine-4-carboxylate

Product 1

HCID 131735383tert-butyl (2R,5R)-2-ethynyl-5-(tert-butyldimethylsilyloxy-methyl)morpholine-4-carboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dimethyl (1-diazo-2-oxpropyl)phosphonate (3.90 mL, 26.0 mmol) was added to tert-butyl (2S,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-formylmorpholine-4-carboxylate (Example 1, step 6) (7.78 g, 21.6 mmol) and K2CO3 (5.98 g, 43.3 mmol) in anhydrous MeOH (216 mL) at ambient temperature. The reaction was stirred for 2 hours then filtered and concentrated in vacuo. Saturated aqueous KH2PO4 was added and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. Purification on silica gel (750 g) eluting with a gradient of 0-30% EtOAc/hexanes afforded the title compound (4.60 g, 12.9 mmol, 60% yield) as a colorless oil, MS (ESI): m/z=256.01 (M+H-Boc).

Workup

  1. filtrationthen filtered
  2. concentrationconcentrated in vacuo
  3. additionSaturated aqueous KH2PO4 was added
  4. extractionthe mixture was extracted with ethyl acetate (×3)
  5. dry with materialThe combined organic fractions were dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customPurification on silica gel (750 g)
  9. washeluting with a gradient of 0-30% EtOAc/hexanes

Sources & evidence

ORD record
ord-52a1b314af60434b8b7d6b15c1ada4f9
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Reaction notes

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