Diethyl Ether → HCID 86598010, compound

HRID 970058Notes

Reaction equation

HRID 970058 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][CH2:14][C:15]1[CH:20]=[C:19]([CH3:21])[C:18]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[C:17]([O:31][CH3:32])[CH:16]=1)[CH2:10][C:11]#N)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[O:35]CC>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][CH2:14][C:15]1[CH:20]=[C:19]([CH3:21])[C:18]([O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[C:17]([O:31][CH3:32])[CH:16]=1)[CH2:10][CH:11]=[O:35])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 3283Diethyl EtherHCID 69434928HCID 69434928, compound

Product 1

HCID 86598010HCID 86598010, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-60 °C

Procedure

A solution of 220 mg (0.49 mmol) of 3-(R)-[N-(tert-butoxycarbonyl)amino]-5-(3-methoxy-5-methyl-4-octyloxyphenyl)-pentanenitrile (from Step D) in 10 mL of Et2O at −60° C. was treated with 2.0 mL (2.0 mmol) of 1M Dibal in toluene over 4 h via a syring pump. After stirring for 1 h additional at −60° C., the reaction was quenched with MeOH and warmed to room temperature. The mixture was poured into 50 mL of saturated NH4Cl (pH adjusted to 3 with 2 N HCl). After separating phases, the aqueous layer was extracted with 2×50 mL of EtOAc (aqueous pH maintained at 3 to avoid an emulsion). The combined organics were dried over Na2SO4 and concentrated. The residue was purified by flash chromatography eluting with 4/1 v/v hexane/EtOAc to afford 95 mg of the title compound as a colorless film. RF: 0.20 (4/1 v/v hexane/EtOAc); 1H-NMR (500 MHz) δ 0.91 (t, J=6.9, 3H), 1.27-1.86 (m, 23H), 2.25 (s, 3H), 2.54-2.70 (m, 4H), 3.84 (s, 3H), 3.89 (t, J=6.8, 2H), 4.08 (m, 1H), 4.72 (m, 1H), 6.57-6.58 (m, 2H), 9.77 (s, 1H).

Workup

  1. customthe reaction was quenched with MeOH
  2. temperaturewarmed to room temperature
  3. additionThe mixture was poured into 50 mL of saturated NH4Cl (
  4. customAfter separating phases
  5. extractionthe aqueous layer was extracted with 2×50 mL of EtOAc (aqueous pH
  6. temperaturemaintained at 3
  7. dry with materialThe combined organics were dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography
  10. washeluting with 4/1 v/v hexane/EtOAc

Sources & evidence

ORD record
ord-b1e1bb173959483b8996d80f59bee228
Source dataset
uspto-grants-2007_12
Patent number
US07309721B2

Reaction notes

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