3-Boc-1,2,3-oxathiazolidine 2,2-dioxide → HCID 68183265, compound

HRID 1615570Notes

Reaction equation

HRID 1615570 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][C:7]2[CH:11]=[C:10]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[S:9][C:8]=2[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:4][CH:3]=1.C[Si](C)(C)N[Si](C)(C)C.[Na].O1[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])S1(=O)=O>CN(C)C=O.O1CCCC1>[C:43]([O:42][C:40]([NH:37][CH2:38][CH2:39][CH:6]([C:7]1[CH:11]=[C:10]([N:12]2[CH2:13][CH2:14][O:15][CH2:16][CH2:17]2)[S:9][C:8]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:24][CH:23]=1)=[O:41])([CH3:46])([CH3:45])[CH3:44].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[CH:11]=[C:10]([N:12]3[CH2:13][CH2:14][O:15][CH2:16][CH2:17]3)[S:9][C:8]=2[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 235840203-Boc-1,2,3-oxathiazolidine 2,2-dioxideHCID 45051731Sodium hexamethyidisilazaneHCID 68182976HCID 68182976, compound

Product 2

HCID 68182976HCID 68182976, compoundYield 35%HCID 68183265HCID 68183265, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Glasswares were flame-dried before use. A solution of ethyl 3-(4-chlorobenzyl)-5-morpholin-4-ylthiophene-2-carboxylate (0.872 g, 2.38 mmol) in N,N-dimethylformamide (16.0 mL) and tetrahydrofuran (4.00 mL) was cooled to −78° C. with vigorous stirring. The solution was evacuated under highvac and purged with argon (×4). 1.00 M Sodium hexamethyldisilazane in tetrahydrofuran (2.62 mL, 2.62 mmol) was added; the solution turned deep purple. The mixture was stirred at −78° C. under argon for 10 min. A solution of tert-butyl 1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (1.06 g, 4.77 mmol) in N,N-dimethylformamide (4.00 mL) was added dropwise over −1 min. The solution turned light red, and then slightly dark green in −1 min. In 15 min, the reaction was warmed to 0° C., and then in 1 h, it was warmed to rt. After 15 min of stirring at rt, the reaction was quenched and distributed between NH4Cl saturated solution and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined organic layer was washed with 10% LiCl aqueous solution (×2) and brine, dried, and concentrated. Purification on a silica gel column (continuous gradient from 5% EtOAc/hexanes to 25% EtOAc/hexanes over 30 min) provided 776 mg of ethyl 3-{3-[(tert-butoxycarbonyl)amino]-1-(4-chlorophenyl)propyl}-5-(morpholin-4-yl)thiophene-2-carboxylate (64% yield) and 303 mg of unreacted ethyl 3-(4-chlorobenzyl)-5-morpholin-4-ylthiophene-2-carboxylate (35% yield). LCMS: (AA) ES+ 510, 512; 1H NMR (400 MHz, CDCl3) δ 7.24-7.21 (s, 4H), 5.88-5.82 (s, 1H), 5.21-5.11 (t, J=7.8 Hz, 1H), 5.06-4.94 (s, 1H), 4.34-4.22 (qd, J=7.1, 2.8 Hz, 2H), 3.83-3.73 (t, J=4.9 Hz, 4H), 3.29-3.19 (s, 1H), 3.22-3.12 (t, J=4.9 Hz, 4H), 2.99-2.85 (m, 1H), 2.25-2.12 (d, J=6.6 Hz, 1H), 2.12-2.06 (s, 1H), 1.47-1.41 (s, 9H), 1.36-1.31 (m, 3H).

Workup

  1. customGlasswares were flame-dried before use
  2. customThe solution was evacuated under highvac and
  3. custompurged with argon (×4)
  4. waitslightly dark green in −1 min
  5. waitIn 15 min
  6. temperaturethe reaction was warmed to 0° C.
  7. waitin 1 h
  8. temperatureit was warmed to rt
  9. stirringAfter 15 min of stirring at rt
  10. customthe reaction was quenched
  11. extractionThe aqueous layer was extracted with EtOAc (×2)
  12. washThe combined organic layer was washed with 10% LiCl aqueous solution (×2) and brine
  13. customdried
  14. concentrationconcentrated
  15. customPurification on a silica gel column (continuous gradient from 5% EtOAc/hexanes to 25% EtOAc/hexanes over 30 min)

Sources & evidence

ORD record
ord-c5819fb7187a41f094a4ee481bc6db4e
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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