HCID 86653081, compound → HCID 67191992, compound

HRID 1254314Notes

Reaction equation

HRID 1254314 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:22]=[O:23])[CH2:10][N:11]([CH3:21])[C:12](=[O:20])[O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:24]1([Mg]Cl)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:10][N:11]([CH3:21])[C:12]([O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[O:20])[C@@H:22]([CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[OH:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 86653081HCID 86653081, compoundHCID 178478990HCID 178478990, compound

Product 1

HCID 67191992HCID 67191992, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of above crude (2-(trimethylsilyl)ethyl) (R)-2-(t-butoxycarbonylamino)-2-formylethylmethylcarbamate (0.71 g, 2.05 mmol) in toluene (6 mL) at −78° C. was added cyclohexylmagnesium chloride (2 M in ether, 5.13 mL) dropwise. The resulting solution was stirred at −78° C. for 1 h, allowed to warm slowly to rt, and quenched with sat'd aq NH4Cl (5 mL). The organic layer was separated, and aqueous layer was extracted with ether (2×5 mL). The combined organic layers were concentrated in vacuo, and the residue was purified by flash column chromatography to give (1R,2R)-2-(t-butoxycarbonylamino)-1-cyclohexyl-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-1-ol (209.7 mg, 24%). 1H NMR (400 MHz, CDCl3): 4.94 (d, 1 H), 4.16 (m, 2 H), 3.80 (m, 1 H), 3.78 (m, 1H), 3.04 (m, 1H), 2.88 (m, 1 H), 2.86 (s, 3 H), 2.10 (m, 1 H), 1.64 (m, 4 H), 1.42 (m, 1 H), 1.40 (s, 9 H), 1.28-1.02 (m, 4 H), 0.98 (m, 2 H), 0.82 (m, 4 H), 0.02 (s, 9 H); MS m/z 431 (M+H+).

Workup

  1. temperatureto warm slowly to rt
  2. customquenched with sat'd aq NH4Cl (5 mL)
  3. customThe organic layer was separated
  4. extractionaqueous layer was extracted with ether (2×5 mL)
  5. concentrationThe combined organic layers were concentrated in vacuo
  6. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-f39e8acca65645399a6f9c45f247da8d
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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