Diisopropylethylamine → N-[2-chloro-4-[[[[3-[[(1,1-dimethylethyl) dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylbenzoyl]-3-[[(1,1-dimethylethoxy)carbonyl]amino]-L-alanine, methyl ester

HRID 393056Notes

Reaction equation

HRID 393056 reaction equation
C(N(C(C)C)CC)(C)C.[Cl:10][C:11]1[CH:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH:25]=2)=[O:21])[CH:17]=[C:16]([CH3:38])[C:12]=1[C:13]([OH:15])=O.Cl.[CH3:40][C:41]([CH3:54])([O:43][C:44]([NH:46][CH2:47][C@@H:48]([C:50]([O:52][CH3:53])=[O:51])[NH2:49])=[O:45])[CH3:42].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>ClCCl.C(OCC)(=O)C>[Cl:10][C:11]1[CH:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][Si:31]([C:34]([CH3:36])([CH3:35])[CH3:37])([CH3:32])[CH3:33])[CH:25]=2)=[O:21])[CH:17]=[C:16]([CH3:38])[C:12]=1[C:13]([NH:49][C@H:48]([C:50]([O:52][CH3:53])=[O:51])[CH2:47][NH:46][C:44]([O:43][C:41]([CH3:54])([CH3:42])[CH3:40])=[O:45])=[O:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 18334328methyl (2S)-2-amino-3-{[(tert-butoxy)carbonyl]amino}propanoate hydrochlorideHCID 226614102-Chloro-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylbenzoic acid

Product 1

HCID 131723026N-[2-chloro-4-[[[[3-[[(1,1-dimethylethyl) dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylbenzoyl]-3-[[(1,1-dimethylethoxy)carbonyl]amino]-L-alanine, methyl esterYield 81.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diisopropylethylamine (2.11 mL, 12.1 mmol) was added to a solution of 2-chloro-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylbenzoic acid (Example 33; 1.32 g, 3.04 mmol) and 3-[[(1,1-dimethylethoxy)carbonyl]amino]-L-alanine, methyl ester, hydrochloride (1.54 g, 6.05 mmol) in dichloromethane (15 mL). Benzotriazol-1-yloxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent; 1.48 g, 3.35 mmol) was added and the mixture was stirred at room temperature for 4 h. The solution was diluted with ethyl acetate, washed with 1 M HCl, water, saturated aqueous sodium hydrogen carbonate, and water. The solution was then dried (MgSO4), filtered, evaporated, and chromatographed (40% ethyl acetate/petroleum ether) to give N-[2-chloro-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylbenzoyl]-3-[[(1,1-dimethylethoxy)carbonyl]amino]-L-alanine, methyl ester (1.57 g, 81%) as a white foam

Workup

  1. washwashed with 1 M HCl, water, saturated aqueous sodium hydrogen carbonate, and water
  2. dry with materialThe solution was then dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customchromatographed (40% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-c0a940f8807948e38b201e118d8e32e0
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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