1,2-Dichloroethane → (R)-benzyl 2-(tert-butoxycarbonylamino)-2-(1-methylcyclohexyl)acetate

HRID 537380Notes

Reaction equation

HRID 537380 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1([CH3:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.[CH2:23](O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(Cl)CCl>CN(C)C1C=CN=CC=1.CCOCC>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]1([CH3:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([O:12][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 244Benzyl AlcoholHCID 6344DichloromethaneHCID 67052824(2R)-2-(tert-butoxycarbonylamino)-2-(1-methylcyclohexyl)acetic acid

Product 1

HCID 86678253(R)-benzyl 2-(tert-butoxycarbonylamino)-2-(1-methylcyclohexyl)acetate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolvent

Procedure

A 2-dram vial containing a small stirbar was charged with (R)-2-(tert-butoxycarbonylamino)-2-(1-methylcyclohexyl)acetic acid (10d) (11 mg, 0.04 mmol), CH2Cl2 (1 mL), 4-dimethylaminopyridine (2 mg, 0.02 mmol, 0.5 equiv), benzyl alcohol (20 μL, 0.2 mmol, 5 equiv), and EDC (20 mg, 0.1 mmol, 2.5 equiv). The solution was stirred at room temperature for 3 h, and then diluted with 10 mL Et2O. The mixture was washed with water (2×10 mL), saturated aqueous NaHCO3 (10 mL), and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (7:1 hexanes/Et2O) and analyzed by chiral HPLC analysis: (AS-H, 1 mL/min, 2% IPA/hexanes, 210 nm): tR(minor)=6.84 min, tR(major)=8.13 min.

Workup

  1. additionA 2-dram vial containing a small stirbar
  2. washThe mixture was washed with water (2×10 mL), saturated aqueous NaHCO3 (10 mL), and brine (10 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography on silica gel (7:1 hexanes/Et2O)
  6. custom=6.84 min
  7. customtR(major)=8.13 min.

Sources & evidence

ORD record
ord-54465fac42764137936b7e1dbd6c6527
Source dataset
uspto-grants-2014_10
Patent number
US08859812B2

Reaction notes

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