Diisopropylethylamine → HCID 68978670, compound

HRID 749424Notes

Reaction equation

HRID 749424 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:19][CH:20]=O)[CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:4][CH:3]=1.[NH:22]1[CH2:25][CH:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH2:23]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([CH2:19][CH2:20][N:22]2[CH2:25][CH:24]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[CH2:23]2)[CH2:9][N:10]([CH3:18])[C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 134019734-(Azetidin-3-yl)morpholineHCID 86606879HCID 86606879, compound

Product 1

HCID 68978670HCID 68978670, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl [(2S)-2-(4-fluorophenyl)-4-oxobutyl]methylcarbamate (1.57 g, 5.3 mmol) and 4-azetidin-3-ylmorpholine (0.83 g, 5.8 mmol) were dissolved in CH2Cl2 (60 mL) together with DIPEA (1.4 g, 10.6 mmol). The mixture was stirred for 20 min and then sodium triacetoxyborohydride (1.6 g, 7.4 mmol) was added. The mixture was stirred at room temperature for 6 h and then the solvent was removed by evaporation. The residue was partitioned between an aqueous solution of NaHCO3 and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the organic solution was dried over MgSO4 and then removed by evaporation. The product was chromatographed on a silica gel using a mixture of methanol and CH2Cl2 (5%-20% methanol) and there was obtained 440 mg (20%) tert-butyl [(2S)-2-(4-fluorophenyl)-4-(3-morpholin-4ylazetidin-1-yl)butyl]methylcarbamate as an oil. 1H NMR (400 MHz, CDCl3): 1.3 (s, 9H), 1.4-1.6 (m, 2H), 2.1-2.3 (b, 5H), 2.5-3.8 (cm, 16H), 6.9 (t, 2H), 7.0-7.1 (b, 2H); LCMS: m/z 422 (M+1)+.

Workup

  1. stirringThe mixture was stirred at room temperature for 6 h
  2. customthe solvent was removed by evaporation
  3. customThe residue was partitioned between an aqueous solution of NaHCO3 and ethyl acetate
  4. extractionThe aqueous phase was extracted with ethyl acetate
  5. dry with materialthe organic solution was dried over MgSO4
  6. customremoved by evaporation
  7. customThe product was chromatographed on a silica gel using
  8. additiona mixture of methanol and CH2Cl2 (5%-20% methanol)

Sources & evidence

ORD record
ord-2d529561761046a49553044b3b7d954b
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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