Bromoacetic Acid → HCID 67415695, compound

HRID 2261453Notes

Reaction equation

HRID 2261453 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12]([C:14]2[S:21][C:20]([CH3:22])=[C:19]3[C:15]=2[CH2:16][C@H:17]2[C:23]([CH3:25])([CH3:24])[C@H:18]23)=[O:13])[CH:5]=[C:6]([CH3:9])[C:7]=1[OH:8].Br[CH2:27][C:28]([OH:30])=[O:29]>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12](=[O:13])[C:14]2[S:21][C:20]([CH3:22])=[C:19]3[C:15]=2[CH2:16][C@H:17]2[C:23]([CH3:25])([CH3:24])[C@H:18]23)[CH:5]=[C:6]([CH3:9])[C:7]=1[O:8][CH2:27][C:28]([OH:30])=[O:29]

Participants

6

Reactant 2

HCID 6227Bromoacetic Acid2×HCID 59593550HCID 59593550, compound2×

Product 1

HCID 67415695HCID 67415695, compoundYield 14.7%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent2×

Conditions

Temperature
70 °C

Procedure

A solution of 3-(3,5-dimethyl-4-hydroxy-phenyl)-1-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propan-1-one (350 mg, 0.988 mmol, Intermediate 10) in isopropanol (5 mL) and 3 N aq. NaOH (1.5 mL) is treated with bromoacetic acid (274 mg, 1.98 mmol). The dark red reaction mixture is stirred at 70° C. After 1, 2, 3 and 18 h an additional portion of bromoacetic acid (274 mg, 1.98 mmol) and 3N aq. NaOH (1.5 mL) is added and stirring is continued for 2 h after the last addition. The reaction mixture is diluted with EA, and washed with 1 N aq. HCl. The aq. phase is extracted with EA. The combined organic extracts are dried over MgSO4 and evaporated. The crude product is purified by chromatography on prep. TLC plates with DCM containing 10% of methanol to give {2,6-dimethyl-4-[3-oxo-3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propyl]-phenoxy}-acetic acid (60 mg) as a pale yellow oil; LC-MS: tR=1.07 min, [M+1]+=413.23.

Workup

  1. customThe dark red reaction mixture
  2. stirringstirring
  3. additionafter the last addition
  4. washwashed with 1 N aq. HCl
  5. extractionThe aq. phase is extracted with EA
  6. dry with materialThe combined organic extracts are dried over MgSO4
  7. customevaporated
  8. customThe crude product is purified by chromatography on prep

Sources & evidence

ORD record
ord-d5d2a3cf9c7a457798d0acde9290f325
Source dataset
uspto-grants-2010_12
Patent number
US07846964B2

Reaction notes

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