Tetrahydrofuran → HCID 87567414, compound

HRID 2054779Notes

Reaction equation

HRID 2054779 reaction equation
[Si:1]([O:8][CH2:9][CH:10]([N:13]([CH2:21]N(OC)C)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:11]=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:26]1([Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1C[O:37]CC1>>[Si:1]([O:8][CH2:9][CH:10]([N:13]([CH:21]=[O:37])[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[CH2:11][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 87567608HCID 87567608, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 87567414HCID 87567414, compoundYield 65%

Conditions

Temperature
0 °C

Procedure

tert-butyl 3-(tert-butyldimethylsilyloxy)-1 (methoxy(methyl)amino)-1-oxopropan-2-ylmethylcarbamate (35) (2.2 g, 5.7 mmol, 1.0 equiv.) was added to a 250 mL RBF followed by THF (60 mL). The mixture was cooled to 0° C. via an ice bath and a 1.0 M solution of PhMgBr in THF (11.5 mL, 11.5 mmol, 2.0 equiv.) was added over 5 min. The reaction stirred for 2.25 h at 0° C. and was quenched by addition of 0.5 M HCl (60 mL). The solution was transferred to a separatory funnel with additional 0.5 M HCl (20 mL) and extracted with EtOAc (3×60 mL). The organic layers were combined, washed with sat. NaCl (1×50 mL), and dried over Na2SO4. The solution was concentrated on a rotary evaporator and dried under vacuum to give 2.8 g of crude material. The residue was purified by flash column chromatography (5% EtOAc/Hexanes) to give 1.5 g (65%) of 36 as an oil. Rf=0.23 (5% EtOAc/Hexanes); IR (film) 2954, 2928, 2855, 1687, 1390, 1148, 1120 cm−1; 1H NMR (500 MHz, CDCl3) δ Major rotamer: 8.01 (d, J=7.5 Hz, 1H, Ph-H), 7.91 (d, J=7.5 Hz, 1H, Ph-H), 7.55 (t, J=7.0 Hz, 1H, Ph-H), 7.47 (m, 2H, Ph-H), 5.60 (m, 1H, Boc-N—CH), 4.14 (m, 1H, CH—CH2), 4.04 (m, 1H, CH—CH2), 2.75 (s, 3H, Boc-N—CH3), 1.41 (s, 9H, Boc-t-butyl-CH3), 0.90 (s, 9H, Si-t-butyl-CH3), 0.06 (s, 3H, Si—CH3), 0.04 (s, 3H, Si—CH3). Minor rotamer: 5.13 (m, 1H, Boc-N—CH), 2.91 (s, 3H, Boc-N—CH3), 1.43 (s, 9H, Boc-t-butyl-CH3), 0.87 (s, 9H, Si-t-butyl-CH3), 0.08 (s, 3H, Si—CH3), 0.06 (s, 3H, Si—CH3); 13C NMR (125 MHz, CDCl3) δ 198.9, 198.1, 155.9, 155.0, 136.1, 133.3, 128.7, 128.6, 128.5, 128.3, 80.9, 80.2, 63.2, 61.1, 60.8, 60.3, 32.7, 31.1, 28.5, 26.0, 25.9, 18.4, 18.3, −5.3, −5.4, −5.5; LRMS (ESI-MS m/z): Mass calcd for C20H33NO4Si [M]+, 393.59. Found 394.

Workup

  1. customwas quenched by addition of 0.5 M HCl (60 mL)
  2. customThe solution was transferred to a separatory funnel with additional 0.5 M HCl (20 mL)
  3. extractionextracted with EtOAc (3×60 mL)
  4. washwashed with sat. NaCl (1×50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationThe solution was concentrated on a rotary evaporator
  7. customdried under vacuum
  8. customto give 2.8 g of crude material
  9. customThe residue was purified by flash column chromatography (5% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-80f6f208dc7d4b109b006483ec5e0147
Source dataset
uspto-grants-2008_02
Patent number
US07329775B2

Reaction notes

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