Triethylamine → tert-butyl [(2S)-2-(3,4-dichlorophenyl)-4-(3-thiomorpholin-4-ylazetidin-1-yl)butyl]methylcarbamate

HRID 749420Notes

Reaction equation

HRID 749420 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:20][CH:21]=O)[CH2:10][N:11]([CH3:19])[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[NH:24]1[CH2:27][CH:26]([N:28]2[CH2:33][CH2:32][S:31][CH2:30][CH2:29]2)[CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>ClCCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:20][CH2:21][N:24]2[CH2:27][CH:26]([N:28]3[CH2:33][CH2:32][S:31][CH2:30][CH2:29]3)[CH2:25]2)[CH2:10][N:11]([CH3:19])[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 15433413tert-Butyl [(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]methylcarbamateHCID 533995614-Azetidin-3-ylthiomorpholine hydrochloride

Product 1

HCID 86606876tert-butyl [(2S)-2-(3,4-dichlorophenyl)-4-(3-thiomorpholin-4-ylazetidin-1-yl)butyl]methylcarbamateYield 31%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

tert-Butyl [(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]methylcarbamate (see WO 95/05377; 610 mg, 1.8 mmol) was dissolved in 1,2-dichloroethane (20 mL) and to the resultant solution was added 4-azetidin-3-ylthiomorpholine hydrochloride (430 mg, 1.9 mmol) followed by the addition of sodium triacetoxyborohydride (480 mg, 2.2 mmol). The mixture was stirred at room temperature for 5 h and then triethylamine (0.73 mL, 5.2 mmol) was added. The reaction mixture was stirred for 2 h and then partitioned between CH2Cl2 and NaHCO3 aq. The organic layer was washed with water and the combined organic solutions were dried over MgSO4. The solvent was removed by evaporation to yield an oil, which was chromatographed on a reversed phase column using a mixture of acetonitrile and 0.1 M ammonium acetate aq. The appropriate fractions were extracted with ether. The organic solution was dried over MgSO4 and then the solvent was removed by evaporation. There was obtained 266 mg (31%) of tert-butyl [(2S)-2-(3,4-dichlorophenyl)-4-(3-thiomorpholin-4-ylazetidin-1-yl)butyl]methylcarbamate as an oil. 1H NMR (400 MHz, CDCl3): 1.4 (s, 9H), 1.5-3.5 (c m, 23H), 7.0 (dd, 1H), 7.3 (d, 1H), 7.4 (d, 1H); LCMS: m/z 488 (M+1)+.

Workup

  1. stirringThe reaction mixture was stirred for 2 h
  2. custompartitioned between CH2Cl2 and NaHCO3 aq. The organic layer
  3. washwas washed with water
  4. dry with materialthe combined organic solutions were dried over MgSO4
  5. customThe solvent was removed by evaporation
  6. customto yield an oil, which
  7. customwas chromatographed on a reversed phase column
  8. additiona mixture of acetonitrile and 0.1 M ammonium acetate aq. The appropriate fractions
  9. extractionwere extracted with ether
  10. dry with materialThe organic solution was dried over MgSO4
  11. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-3334652eaffe4cecbae8d05ff5a5d5ab
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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