3-Bromo-1-propanol → HCID 67415421, compound

HRID 2261455Notes

Reaction equation

HRID 2261455 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:11][CH2:12][C:13]([C:15]2[S:22][C:21]([CH3:23])=[C:20]3[C:16]=2[CH2:17][C@H:18]2[C:24]([CH3:26])([CH3:25])[C@H:19]23)=[O:14])[CH:5]=[C:6]([O:9][CH3:10])[C:7]=1[OH:8].Br[CH2:28][CH2:29][CH2:30][OH:31]>C(O)(C)C.[OH-].[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:11][CH2:12][C:13]([C:15]2[S:22][C:21]([CH3:23])=[C:20]3[C:16]=2[CH2:17][C@H:18]2[C:24]([CH3:26])([CH3:25])[C@H:19]23)=[O:14])[CH:5]=[C:6]([O:9][CH3:10])[C:7]=1[O:8][CH2:28][CH2:29][CH2:30][OH:31]

Participants

5

Reactant 2

HCID 123083-Bromo-1-propanol2×HCID 59593509HCID 59593509, compound2×

Product 1

HCID 67415421HCID 67415421, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-(3-chloro-4-hydroxy-5-methoxy-phenyl)-1-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propan-1-one (800 mg, 2.05 mmol, Intermediate 14) in isopropanol (30 mL) and 2 N aq. NaOH (10 mL) is treated with 3-bromopropanol (569 mg, 4.09 mmol). The dark red reaction mixture is stirred at 70° C. After 4.5 and 22 h another portion of 3-bromopropanol (569 mg, 4.09 mmol) is added. Stirring is continued for further 2 h after the last addition. The solvent is removed under reduced pressure and the residue is dissolved in EA and washed twice with water. The organic layer is dried over MgSO4 and evaporated. The crude product is purified by CC on silica gel eluting with heptane:EA 1:1 to give 3-[3-chloro-4-(3-hydroxy-propoxy)-5-methoxy-phenyl]-1-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propan-1-one (460 mg) as a yellow oil; LC-MS: tR=1.10 min, [M+1]+=449.22; 1H NMR (CDCl3): δ 676-674 (m, 1H), 6.64-6.61 (m, 1H), 4.05 (t, J=5.5 Hz, 2H), 3.90-3.85 (m, 2H), 3.77 (s, 3H), 3.01-2.85 (m, 5H), 2.72 (d, J=18.8 Hz, 1H), 2.31 (s, 3H), 1.98-1.90 (m, 2H), 1.85-1.80 (m, 2H), 1.05 (s, 3H), 0.63 (s, 3H).

Workup

  1. customThe dark red reaction mixture
  2. stirringStirring
  3. additionafter the last addition
  4. customThe solvent is removed under reduced pressure
  5. dissolutionthe residue is dissolved in EA
  6. washwashed twice with water
  7. dry with materialThe organic layer is dried over MgSO4
  8. customevaporated
  9. customThe crude product is purified by CC on silica gel eluting with heptane:EA 1:1

Sources & evidence

ORD record
ord-01baccd0a65f49ab83485a87d59a25c2
Source dataset
uspto-grants-2010_12
Patent number
US07846964B2

Reaction notes

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