9-Fluorenylmethyl chloroformate → (2R,3S)-3-(t-butoxycarbonylamino)-4-cyclohexyl-1-(N-(3,5-dimethoxybenzyl)-N-((9H-fluoren-9-yl)methoxycarbonyl)amino)butan-2-ol

HRID 253563Notes

Reaction equation

HRID 253563 reaction equation
[CH:1]1([CH2:7][C@H:8]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C@H:9]([OH:23])[CH2:10][NH:11][CH2:12][C:13]2[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.Cl[C:42]([O:44][CH2:45][CH:46]1[C:58]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[C:52]2[C:47]1=[CH:48][CH:49]=[CH:50][CH:51]=2)=[O:43]>C(Cl)Cl>[C:27]([O:26][C:25]([NH:24][C@@H:8]([CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[C@H:9]([OH:23])[CH2:10][N:11]([CH2:12][C:13]1[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[C:15]([O:21][CH3:22])[CH:14]=1)[C:42]([O:44][CH2:45][CH:46]1[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:52]=2[C:53]2[C:58]1=[CH:57][CH:56]=[CH:55][CH:54]=2)=[O:43])=[O:31])([CH3:28])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 343679-Fluorenylmethyl chloroformateHCID 81531DiisopropylethylamineHCID 57786530tert-butyl (2S,3R)-1-cyclohexyl-4-(3,5-dimethoxybenzylamino)-3-hydroxybutan-2-ylcarbamate

Product 1

HCID 57786493(2R,3S)-3-(t-butoxycarbonylamino)-4-cyclohexyl-1-(N-(3,5-dimethoxybenzyl)-N-((9H-fluoren-9-yl)methoxycarbonyl)amino)butan-2-olYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (2S,3R)-1-cyclohexyl-4-(3,5-dimethoxybenzylamino)-3-hydroxybutan-2-ylcarbamate (66.5 mg, 0.153 mmol) in CH2Cl2 (10 mL) at 0° C. was added DIEA (1.5 mL) followed by 9-fluorenylmethyl chloroformate (39.5 mg, 0.153 mmol) and the resulting mixture was stirred at 0° C. for 2 h and at rt for 2 h. The reaction mixture was concentrated and the residue was diluted with EtOAc and water. The organics were washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The residue was chromatographed on silica gel to provide (2R,3S)-3-(t-butoxycarbonylamino)-4-cyclohexyl-1-(N-(3,5-dimethoxybenzyl)-N-((9H-fluoren-9-yl)methoxycarbonyl)amino)butan-2-ol (78.5 mg, 78%). 1H NMR: 0.79 (m, 1H), 0.95 (m, 1H), 1.06-1.38 (m, 6H), 1.42 (s, 9H), 1.56-1.70 (m, 6H), 1.83 (m, 1H), 3.25-3.50 (m, 2H), 3.70 (m, 1H), 3.73 (s, 6H), 3.85 (m, 1H), 4.22 (m, 1H), 4.29-4.70 (m, 5H), 6.35 (m, 3H), 7.20 (m, 1H), 7.32-7.48 (m, 4H), 7.58 (m, 1H), 7.69 (m, 1H), 7.75 (m, 1H). MS (E/Z): 659 (M+H+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was diluted with EtOAc and water
  3. washThe organics were washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-48318fb186414fa7a96bf691d832e01b
Source dataset
uspto-grants-2011_01
Patent number
US07872028B2

Reaction notes

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