Chloroacetyl chloride → HCID 131729372, compound

HRID 420293Notes

Reaction equation

HRID 420293 reaction equation
[NH2:1][C:2]1[C:31]([F:32])=[CH:30][C:5]([CH2:6][C@H:7]2[C@H:15]3[C@@H:11]([N:12]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([CH3:27])([CH3:26])[CH3:25])[CH:19]=4)[C:13](=[O:16])[O:14]3)[CH2:10][S:9](=[O:29])(=[O:28])[CH2:8]2)=[CH:4][C:3]=1[CH2:33][CH3:34].CCN(C(C)C)C(C)C.[Cl:44][CH2:45][C:46](Cl)=[O:47].C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:24]([C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=1)[CH2:17][N:12]1[C@@H:11]2[C@H:15]([C@H:7]([CH2:6][C:5]3[CH:30]=[C:31]([F:32])[C:2]([NH:1][C:46](=[O:47])[CH2:45][Cl:44])=[C:3]([CH2:33][CH3:34])[CH:4]=3)[CH2:8][S:9](=[O:28])(=[O:29])[CH2:10]2)[O:14][C:13]1=[O:16])([CH3:26])([CH3:27])[CH3:25]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 66649516HCID 66649516, compound

Product 1

HCID 131729372HCID 131729372, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a solution of (3aR,7S,7aS)-7-(4-amino-3-ethyl-5-fluoro-benzyl)-3-(3-tert-butyl-benzyl)-5,5-dioxo-hexahydro-1-oxa-5lambda*6*-thia-3-aza-inden-2-one (0.245 g, 0.5 mmol) and DIPEA (0.52 mL, 3 mmol) in CH2Cl2 was slowly added a solution of 2-chloroacetylchloride (0.226 g, 2.0 mmol) dissolved in CH2Cl2 (2 mL) at 0-5° C. After stirring for 1 h at 0-5° C. the reaction mixture was poured onto cold saturated NaHCO3 solution and extracted with CH2Cl2. Combined organic extracts were washed with brine, dried over MgSO4, filtered and evaporated. The crude product was dissolved in MeOH, stirred for 0.5 h at 25° C., and evaporated again. The title compound was obtained after chromatographic purification (Combi Flash, 12 g silica gel, hexane-EtOAc) as a light yellow solid: TLC (toluene-EtOAc 1:1) Rf=0.44; UPLC RtD=1.799 min; ESIMS [M+NH4]+=582; 1H NMR (600 MHz, DMSO-d6): δ 9.70 (s, 1H), 7.39 (s, 1H), 7.32 (d, 1H), 7.27 (t, 1H), 7.13 (d, 1H), 6.98 (d, 1H), 6.95 (s, 1H), 4.42 (d, 1H), 4.28 (s, 2H), 4.21 (d, 1H), 4.19 (t, 1H), 3.72 (m, 2H), 3.48 (t, 1H), 3.14 (dd, 1H), 2.98 (m, 2H), 2.55 (m, 4H), 1.26 (s, 9H), 1.08 (t, 3H).

Workup

  1. extractionextracted with CH2Cl2
  2. washCombined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe crude product was dissolved in MeOH
  7. stirringstirred for 0.5 h at 25° C.
  8. customevaporated again

Sources & evidence

ORD record
ord-767c6a3031204bd7b69ace390391a1c7
Source dataset
uspto-grants-2012_01
Patent number
US08093406B2

Reaction notes

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