Chlorotrimethylsilane → HCID 59149921, compound

HRID 655560Notes

Reaction equation

HRID 655560 reaction equation
[OH:1][C@@H:2]1[CH2:9][N:8]([CH2:10][CH2:11][C@H:12]([N:15]2[C:21](=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH2:13][OH:14])[CH2:7][CH2:6][C:3]21[CH2:5][CH2:4]2.C(N(CC)CC)C.Cl[Si](C)(C)C.[Cl:35][C:36]1[CH:37]=[C:38]([N:43]=[C:44]=[O:45])[CH:39]=[CH:40][C:41]=1[Cl:42]>ClCCl.CN(C)C=O>[Cl:35][C:36]1[CH:37]=[C:38]([NH:43][C:44]([N:18]2[CH2:19][CH2:20][C:21](=[O:22])[N:15]([C@H:12]([CH2:13][OH:14])[CH2:11][CH2:10][N:8]3[CH2:7][CH2:6][C:3]4([CH2:4][CH2:5]4)[C@H:2]([OH:1])[CH2:9]3)[CH2:16][CH2:17]2)=[O:45])[CH:39]=[CH:40][C:41]=1[Cl:42]

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 76073,4-Dichlorophenyl isocyanateHCID 8471TriethylamineHCID 67080751HCID 67080751, compound

Product 1

HCID 59149921HCID 59149921, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 0.066 g (0.21 mmol) of 4-[(S)-3-((S)-4-hydroxy-6-aza-spiro[2.5]oct-6-yl)-1-hydroxymethyl-propyl]-[1,4]diazepan-5-one (example 51B) 1.3 ml of N,N-dimethylformamide was treated at room temperature with 0.097 ml (0.70 mmol) of triethylamine and 0.088 ml (0.70 mmol) of chlorotrimethylsilane. The suspension was diluted with 1 ml of dichloromethane and stirred over night at room temperature. A solution of 0.044 g (0.23 mmol) of 3,4-dichlorophenyl isocyanate was added and stirred for 3 h at room temperature. The reaction was evaporated under reduced pressure, redissolved in 2 ml of methanol and 0.2 ml of 1 M aq. hydrochloric acid solution and after 5 min again evaporated. Partitioning between sat. aq. sodium hydrogencarbonate solution and dichloromethane (3×), drying of the organic phase over Na2SO4 and purification by flash silica gel column (dichloromethane/methanol 95:5 to 4:1) yielded 0.065 g (61%) of the title compound as yellow foam. MS: 499.2 (MH+, 2Cl).

Workup

  1. stirringstirred for 3 h at room temperature
  2. customThe reaction was evaporated under reduced pressure
  3. dissolutionredissolved in 2 ml of methanol
  4. custom0.2 ml of 1 M aq. hydrochloric acid solution and after 5 min again evaporated
  5. customPartitioning between sat. aq. sodium hydrogencarbonate solution and dichloromethane (3×)
  6. dry with materialdrying of the organic phase over Na2SO4 and purification by flash silica gel column (dichloromethane/methanol 95:5 to 4:1)

Sources & evidence

ORD record
ord-0c053280e70b485aa18c9603d1aaa96c
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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