Water → HCID 59382849, compound

HRID 451863Notes

Reaction equation

HRID 451863 reaction equation
[Si:1]([O:8][CH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][C@H:16]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:17][NH:18][CH3:19])[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CCN(CC)CC.[C:35](Cl)([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36].O>C(Cl)Cl>[Si:1]([O:8][CH:9]1[CH2:10][CH2:11][CH:12]([CH2:15][C@H:16]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:17][N:18]([CH3:19])[C:35]([O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[O:36])[CH2:13][CH2:14]1)([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 59382970HCID 59382970, compound

Product 1

HCID 59382849HCID 59382849, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl 1-(4-(tert-butyldimethylsilyloxy)cyclohexyl)-3-(methylamino)propan-2-ylcarbamate (57 g, 0.142 mol) and Et3N (28.8 g, 0.285 mol) in CH2Cl2 (600 mL) was added CbzCl (26.6 g, 0.156 mol) at −20° C., which was allowed to stir for 1 h at rt. The reaction mixture was treated with water (200 mL) and extracted with CH2Cl2 (3×100 mL). The organic layer was dried over Na2SO4 and evaporated. The residue was separated on a silica column to give the pure isomer (S)-tert-butyl 1-(4-(tert-butyldimethylsilyloxy)cyclohexyl)-3-(N-methyl-N-(benzyloxycarbonyl)amino)propan-2-ylcarbamate (5.5 g) and a fraction with a mixture isomers (33 g, total yield 51%). Mixture isomer: 1H NMR (CDCl3, 400 MHz) δ 0.02 (d, 6H), 0.88 (s, 9H), 1.16-1.29 (m, 5H), 1.41 (d, 9H), 1.60 (m, 51H), 1.83 (m, 1H), 2.95 (t, 3H), 3.00-3.40 (m, 1H), 3.49 (m, 1H), 3.89 (m, 2H), 5.11 (s, 2H), 7.34 (m, 5H).

Workup

  1. extractionextracted with CH2Cl2 (3×100 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customevaporated
  4. customThe residue was separated on a silica column

Sources & evidence

ORD record
ord-f1030716d1c34c00bc0de161bdc4260f
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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