Methanol → 1-{4-[3-oxo-3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propyl]-benzyl}-azetidine-3-carboxylic acid

HRID 2261440Notes

Reaction equation

HRID 2261440 reaction equation
[O:1]=[C:2]([C:13]1[S:20][C:19]([CH3:21])=[C:18]2[C:14]=1[CH2:15][C@H:16]1[C:22]([CH3:24])([CH3:23])[C@H:17]12)[CH:3]=[CH:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1.[NH:25]1[CH2:28][CH:27]([C:29]([OH:31])=[O:30])[CH2:26]1.CO>C(#N)C.O>[O:1]=[C:2]([C:13]1[S:20][C:19]([CH3:21])=[C:18]2[C:14]=1[CH2:15][C@H:16]1[C:22]([CH3:24])([CH3:23])[C@H:17]12)[CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:9][N:25]2[CH2:28][CH:27]([C:29]([OH:31])=[O:30])[CH2:26]2)=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 931923-azetidinecarboxylic AcidHCID 866225074-[3-oxo-3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propenyl]-benzaldehyde

Product 1

HCID 118530921-{4-[3-oxo-3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propyl]-benzyl}-azetidine-3-carboxylic acidYield 37.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A suspension of 4-[3-oxo-3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propenyl]-benzaldehyde (50 mg, 0.15 mmol), azetidine-3-carboxylic acid (19 mg, 0.19 mmol) and NaHB(OAc)3 (94 mg, 0.45 mmol) in acetonitrile (3 mL) is stirred at rt for 4 h before methanol (1 mL) is added. The clear solution is stirred for 5 min, diluted with water and extracted four times with DCM. The combinded organic extracts are dried over MgSO4 and evaporated. The obtained resin is dissolved in ethanol (5 mL) and THF (5 mL) and treated with a suspension of Pd/C (20 mg, 10% Pd) in ethanol (2 mL). The mixture is stirred at rt for 22 h under 1.5 bar H2. The reaction mixture is filtered and the filtrate is evaporated. The crude product is purified by chromatography on prep. TLC-plates (DCM containing 20% of methanol) to give 1-{4-[3-oxo-3-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propyl]-benzyl}-azetidine-3-carboxylic acid (24 mg) as a beige foam; LC-MS: tR=0.87 min, [M+1]+=424.24; 1H NMR (CDCl3): δ 7.30-7.16 (m, 4H), 4.02-3.70 (m br, 7H), 3.28-3.18 (m, 1H), 3.04-2.90 (m, 3H), 2.76 (d, J=18.8 Hz, 1H), 2.36 (s, 3H), 1.90-1.84 (m, 2H), 1.10 8s, 3H), 0.68 (s, 3H).

Workup

  1. additionis added
  2. extractionextracted four times with DCM
  3. dry with materialThe combinded organic extracts are dried over MgSO4
  4. customevaporated
  5. dissolutionThe obtained resin is dissolved in ethanol (5 mL)
  6. additionTHF (5 mL) and treated with a suspension of Pd/C (20 mg, 10% Pd) in ethanol (2 mL)
  7. stirringThe mixture is stirred at rt for 22 h under 1.5 bar H2
  8. filtrationThe reaction mixture is filtered
  9. customthe filtrate is evaporated
  10. customThe crude product is purified by chromatography on prep

Sources & evidence

ORD record
ord-a0c82e5555ae4d79af7ac9742a732e09
Source dataset
uspto-grants-2010_12
Patent number
US07846964B2

Reaction notes

Loading…