Hydrochloric Acid → HCID 178515811, compound

HRID 1173830Notes

Reaction equation

HRID 1173830 reaction equation
C([Si](C)(C)[O:6][C@@H:7]1[CH2:12][CH2:11][C@H:10]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])[CH2:9][CH2:8]1)(C)(C)C.[Li+].CC([N-]C(C)C)C.Br[CH2:30][C:31]1[S:35][C:34]2[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=2[C:32]=1[Cl:40].Cl>CO.O.C1COCC1>[Cl:40][C:32]1[C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[S:35][C:31]=1[CH2:30][CH:15]1[CH2:16][CH2:17][N:13]([C@H:10]2[CH2:9][CH2:8][C@@H:7]([OH:6])[CH2:12][CH2:11]2)[C:14]1=[O:18]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8167082-(Bromomethyl)-3-chloro-1-benzothiopheneHCID 2724682Lithium diisopropylamideHCID 178455336HCID 178455336, compound

Product 1

HCID 178515811HCID 178515811, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Charge a flask with cis-1-[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-pyrrolidin-2-one (0.50 g, 1.68 mmol) (1.0 eq), dissolve with THF (0.2 M) and cool to −78° C. Add LDA (1.1 to 1.5 eq) and stir at −78° C. for 5 minutes. Add 2-bromomethyl-3-chloro-benzo[b]thiophene (U.S. Pat. No. 4,939,140) (0.53 g, 2.02 mmol) and warm to room temperature overnight. Dilute with methanol (0.2 M) and add concentrated HCl (10 eq.) and stir at room temperature. Pour into water after reaction complete by HPLC and extract with methylene chloride, dry over sodium sulfate, filter and concentrate in vacuo. Purification of the residue over silica gel (20% hexane in ethyl acetate) affords the title compound as a white powder (0.44 g, 71%): MS (APCI-pos mode) m/z (rel intensity) 364.1 (100), 366.1 (40).

Workup

  1. temperature4,939,140) (0.53 g, 2.02 mmol) and warm to room temperature overnight
  2. customafter reaction complete by HPLC
  3. extractionextract with methylene chloride
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurification of the residue over silica gel (20% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-2becacd583fc4e6b955360d28d37b702
Source dataset
uspto-grants-2010_11
Patent number
US07834194B2

Reaction notes

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