Chloroacetyl chloride → HCID 56616541, compound

HRID 375758Notes

Reaction equation

HRID 375758 reaction equation
[NH2:1][C@H:2]1[CH2:13][O:12][C:11](=[O:14])[C:10]2[CH:15]=[C:16]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH:17]=[C:18]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[C:9]=2[CH2:8][S:7][CH2:6][C@@H:5]([C:35]([O:37][CH3:38])=[O:36])[NH:4][C:3]1=[O:39].C(N(CC)CC)C.[Cl:47][CH2:48][C:49](Cl)=[O:50]>C(Cl)Cl>[Si:28]([O:27][C:16]1[CH:17]=[C:18]([O:19][Si:20]([C:23]([CH3:24])([CH3:25])[CH3:26])([CH3:21])[CH3:22])[C:9]2[CH2:8][S:7][CH2:6][C@@H:5]([C:35]([O:37][CH3:38])=[O:36])[NH:4][C:3](=[O:39])[C@@H:2]([NH:1][C:49](=[O:50])[CH2:48][Cl:47])[CH2:13][O:12][C:11](=[O:14])[C:10]=2[CH:15]=1)([C:31]([CH3:32])([CH3:33])[CH3:34])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 56619767HCID 56619767, compound

Product 1

HCID 56616541HCID 56616541, compoundYield 81.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 1.30 g of methyl (4R, 7S)-7-amino-12,14-bis(tert-butyldimethylsilyloxy)-1,3,4,5,6,7,8,10-octahydro-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4 -carboxylate and 0.23 g of triethylamine in 50 ml of methylene chloride, was added at 0° C. within 2 minutes a solution of 0.25 g of chloro-acetyl chloride in 3 ml of methylene chloride. The mixture was stirred at 0° C. for 30 minutes, then diluted with methylene chloride and washed successively with 0.03N hydrochloric acid and water. The organic layer was dried over sodium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1, v/v) as eluent to yield 1.20 g of methyl (4R, 7S)-12,14-bis (tert-butyldimethylsilyloxy)-7-(2-chloroacetamido)-1,3,4,5,6,7,8,10-octahydro-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4-carboxylate as a white solid. A sample of 287 mg of this material was treated with ammonium fluoride in methanol in an analogous manner to the procedure described in Example 13 to yield, after crystallization from ethyl acetate, 115 mg of methyl (4R, 7S)-7-(2chloroacetamido)-1,3,4,5,6,7,8,10-octahydro-12,14-dihydroxy6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-4 -carboxylate as a white solid, m.p. 182° C. (dec.).

Workup

  1. washwashed successively with 0.03N hydrochloric acid and water
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customevaporated in vacuo
  4. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-eb2ff5039977458e860d5f3fce6be097
Source dataset
uspto-grants-1996_01
Patent number
US05486466

Reaction notes

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