Water → HCID 59382849, compound

HRID 2355469Notes

Reaction equation

HRID 2355469 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.Cl[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37].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]([C:36]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37])[CH3:19])[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 80.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture solution of tert-butyl (S)-1-(4-(t-butyldimethylsilyloxy)cyclohexyl)-3-(methylamino)propan-2-ylcarbamate (112 g, 209 mmol) and Et3N (52.8 g, 522 mmol) in CH2Cl2 (1200 mL) was added dropwise a solution of benzyl chloroformate (39 g, 230 mmol) in CH2Cl2 (40 mL) at −20° C. After stirring for an additional 2 h, water (400 mL) was added and the mixture was extracted with CH2Cl2 (2×200 mL). The organic layers were washed with brine, dried over MgSO4, and evaporated. The residue was purified by silica chromatography to afford crude tert-butyl (S)-1-(4-(t-butyldimethylsilyloxy)cyclohexyl)-3-(N-(benzyloxycarbonyl)-N-methylamino)propan-2-ylcarbamate (90 g) as an oil which was a mixture of two isomers. The isomers were separated by preparative HPLC. 1H NMR (CDCl3, 400 MHz): δ=0.08 (s, 6H), 0.89 (s, 9H), 1.28 (m, 4H), 1.40 (d, 9H), 1.59 (m, 4H), 2.96 (d, 3H), 3.05 (d, 1H), 3.15 (d, 1H), 3.45 (t, 3H), 3.90 (s, 1H), 5.12 (d, 2H), 7.33 (m, 5H).

Workup

  1. extractionthe mixture was extracted with CH2Cl2 (2×200 mL)
  2. washThe organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe residue was purified by silica chromatography

Sources & evidence

ORD record
ord-63558e482c77466594c9d875e9203b19
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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