Methanol → Tert-butyl (s,s)-3,3-dimethyl-3-silabutyl 2-(4-((tert-butyl)oxycarbonyl)-2-(2-bromoacetylamino) butanoylamino)pentane-1,5-dioate

HRID 9712Notes

Reaction equation

HRID 9712 reaction equation
[NH2:1][C@@H:2]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:3]([NH:5][C@@H:6]([CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])=[O:17])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[O:4].C(N(C(C)C)CC)(C)C.[Br:43][CH2:44][C:45](Br)=[O:46].CO>O1CCCC1>[C:30]([O:29][C:27]([CH2:26][CH2:25][C@H:2]([NH:1][C:45](=[O:46])[CH2:44][Br:43])[C:3]([NH:5][C@@H:6]([CH2:14][CH2:15][C:16]([O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:22])[CH3:24])=[O:17])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[O:4])=[O:28])([CH3:33])([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 887MethanolHCID 61147Bromoacetyl bromideHCID 81531DiisopropylethylamineHCID 86590842tert-Butyl (S,S)-3,3-Dimethyl-3-silabutyl 2-(2-Amino-4-((tert-butyl)oxycarbonyl)butanoylamino)pentane-1,5-dioate

Product 1

HCID 86590844Tert-butyl (s,s)-3,3-dimethyl-3-silabutyl 2-(4-((tert-butyl)oxycarbonyl)-2-(2-bromoacetylamino) butanoylamino)pentane-1,5-dioateYield 78.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The product of step 7H (397 mg, 0.813 mmol) was dissolved in dry tetrahydrofuran (5 mL) with diisopropylethylamine (180 μL, 1.05 mmol) and cooled to —10° C. under nitrogen. Bromoacetyl bromide (85 μL, 0.98 mmol), dissolved in 10 mL tetrahydrofuran, was added dropwise to the cold solution, keeping T≦−5° C. The reaction was stirred in the cold for 1.5 hr, and 25 μL methanol added. The solids were filtered and rinsed and the combined filtrate concentrated to a brown oil, which was purified by flash chromatography (dichloromethane/ethyl acetate) to afford the product (388 mg, 78%) as a light tan oil. LRMS (ES): 609.3/611.3 [M+H]+, 631.3/633.3 [M+Na]+, 185.3, 144.2. 1HNMR (600.1343 MHz, CDCl3): 7.32 (m, 1H), 7.09 (m, 1H), 4.50 (m, 2H), 4.21 (m, 2H), 3.87 (m, 2H), 2.31 (m, 2H), 2.13 (m, 2H), 1.99 (m, 2H), 1.97 (m, 2H), 1.45 (s, 9H), 1.43 (s, 9H), 1.01 (m, 2H), 0.04 (s, 9H).

Workup

  1. temperaturecooled to —10° C. under nitrogen
  2. additionwas added dropwise to the cold solution
  3. customT≦−5° C
  4. filtrationThe solids were filtered
  5. washrinsed
  6. concentrationthe combined filtrate concentrated to a brown oil, which
  7. customwas purified by flash chromatography (dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-ffa80996e43c4aaca4a7d4ff337d019a
Source dataset
uspto-grants-2006_08
Patent number
US07090828B2

Reaction notes

Loading…