Dimethyl Sulfoxide → Carbamic acid, (2-oxocyclopentyl)-, 1,1-dimethylethyl ester, (S)- (9CI)

HRID 245055Notes

Reaction equation

HRID 245055 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][C@H:12]1[CH2:16][CH2:15][CH2:14][C@@H:13]1[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C>C1COCC1.O>[O:11]=[C:12]1[CH2:16][CH2:15][CH2:14][C@@H:13]1[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 10104271tert-Butyl [(1S,2S)-2-hydroxycyclopentyl]carbamate

Product 1

HCID 10397865Carbamic acid, (2-oxocyclopentyl)-, 1,1-dimethylethyl ester, (S)- (9CI)Yield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-72 °C

Procedure

A mixture of oxalyl chloride (6.47 mL, 74.5 mmol) in THF (166 mL) is cooled to −72° C. under nitrogen and treated dropwise with DMSO (10.59 mL, 149.1 mmol). The mixture is stirred for 5 min, whereupon tert-butyl (1S,2S)-2-hydroxycyclopentylcarbamate (10.0 g, 49.7 mmol) is added. Stirring is continued at −75° C. for 45 min. Triethylamine (37.4 mL, 268.3 mmol) is added slowly keeping the temperature below −68° C. After the addition is complete the reaction is allowed to warm slowly to room temperature overnight. The reaction is combined with the reaction mixture from a pilot reaction (200 mg scale) completed earlier. Water (100 mL) is added and the reaction is concentrated in vacuo to remove THF. The mixture is extracted with EtOAc (3×150 mL). The combined organic portions are dried over sodium sulfate, filtered, and concentrated to give 12.41 g of crude product as a yellow oil. The material is purified on silica gel (330 g, 10-40% EtOAc/hexanes) to give the title compound (9.17 g, 93%). 1H-NMR (400 MHz, CDCl3) δ 5.04-5.02 (m, 1H), 3.98-3.96 (m, 1H), 2.65-2.63 (m, 1H), 2.44-2.39 (m, 1H), 2.21-2.11 (m, 1H), 2.04 (s, 1H), 1.89-1.85 (m, 1H), 1.66-1.59 (m, 1H), 1.44 (s, 9H). GC-MS m/z 199 (M+). [a]D20=+96.9° (c 1.0, CHCl3) [literature (Aube, J.; Wolfe, M. S.; Yantiss, R. K.; Cook, S. M.; Takusagawa, F. Synthetic Communications 1992, 22, 3003-3012) [a]D25=+125° (c 0.2, CHCl3)].

Workup

  1. additionis added
  2. customthe temperature below −68° C
  3. additionAfter the addition
  4. temperatureto warm slowly to room temperature overnight
  5. customThe reaction is combined with the reaction mixture from a pilot reaction (200 mg scale)
  6. concentrationthe reaction is concentrated in vacuo
  7. customto remove THF
  8. extractionThe mixture is extracted with EtOAc (3×150 mL)
  9. dry with materialThe combined organic portions are dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give 12.41 g of crude product as a yellow oil
  13. customThe material is purified on silica gel (330 g, 10-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-25de020a875e42198db5d6cbbe29b88c
Source dataset
uspto-grants-2014_02
Patent number
US08658693B2

Reaction notes

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