Dichloromethane → N-(1-Carbobenzyloxy-5-phthalimidopentyl)-alpha-azaalanyl-(L)-proline-t-butyl ester

HRID 979958Notes

Reaction equation

HRID 979958 reaction equation
[C:1]([O:5][C:6](=[O:17])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:16])[N:13]([CH3:15])[NH2:14])([CH3:4])([CH3:3])[CH3:2].[C:18]1(=[O:44])[N:22]([CH2:23][CH2:24][CH2:25][CH2:26][C:27](=O)[C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[C:21](=[O:39])[C:20]2=[CH:40][CH:41]=[CH:42][CH:43]=[C:19]12.C(Cl)Cl.C([BH3-])#N.[Na+]>C1COCC1.C(O)(=O)C.CO>[C:1]([O:5][C:6](=[O:17])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:16])[N:13]([CH3:15])[NH:14][CH:27]([C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[CH2:26][CH2:25][CH2:24][CH2:23][N:22]1[C:18](=[O:44])[C:19]2=[CH:43][CH:42]=[CH:41][CH:40]=[C:20]2[C:21]1=[O:39])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 5003444Sodium cyanoborohydrideHCID 14537397Azaalanyl proline t-butyl esterHCID 20193470Benzyl 6-phthalimido-2-oxohexanoate

Product 1

HCID 18606049N-(1-Carbobenzyloxy-5-phthalimidopentyl)-alpha-azaalanyl-(L)-proline-t-butyl esterYield 73%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of carbazide 2 (0.665 g; 2.74 mmol) and benzyl 6-phthalimido-2-oxohexanoate (1.00 g; 2.74 mmol) in THF (5 ml) containing glacial acetic acid (3 drops) was heated at reflux for 3 hours. TLC (silica gel, CH2Cl2 --CH3OH,20:1) showed a single product spot, Rf=0.5. The crude product was treated as for 14 (Example 10) with sodium cyanoborohydride (172 mg; 2.74 mmol), giving pure carbazide 24 (1.18 g; 2.00 mmol; 73%) after flash chromatography on silica gel (hexanes-EtAc, 1:1). TLC (silica gel; hexanes-EtOAc, 1:1) showed a mixture (1:1) of diastereomers, Rf=0.25, 0.30. MS m/e 592 (M+). Analysis: Calculated for C32H40N4O7 : C, 64.85; H, 6.80; N, 9.45. Found: C, 64.24; H, 6.98; N, 8.95. NMR (CDCl3): δ 1.40 (9H,s); 1.5-2.0 (8H,m); 2.88, 2.90 (3H,2 x S); 3.2-3.7 (6H,m); 4.2-4.4 (1H,m); 4.8-5.1 (1H,m); 5.12, 5.15 (2H,2 x S); 7.27 (5H,s); 7.6-7.9 (4H,m). IR (CHCl3): 2980, 1770, 1730, 1720, 1640 cm-1.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hours

Sources & evidence

ORD record
ord-4428435d61f44814922a735d5a50ed2a
Source dataset
uspto-grants-1987_01
Patent number
US04634715

Reaction notes

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