Pyridine → HCID 89676698, compound

HRID 926201Notes

Reaction equation

HRID 926201 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH3:12])[C:3]=1[C@H:13]([O:35][C:36]([CH3:40])([CH3:39])[CH2:37][OH:38])[CH2:14][O:15][C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH3:41][C:42](OC(C)=O)=[O:43].N1C=CC=CC=1.C([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.CCOC(C)=O.O>[C:42]([O:38][CH2:37][C:36]([O:35][C@@H:13]([C:3]1[C:4]([CH3:12])=[CH:5][C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]=1[Cl:1])[CH2:14][O:15][C:16]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)([CH3:40])[CH3:39])(=[O:43])[CH3:41]

Participants

8

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 89677388(S)-2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropan-1-ol

Product 1

HCID 89676698HCID 89676698, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

At 23° C., a flask containing (S)-2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropan-1-ol (1.31 g, 2.21 mmol) was charged with Ac2O (5.00 mL) immediately followed by pyridine (5.00 mL). 4-(N,N-dimethylamino)-pyridine (20 mg, 0.164 mmol) was added. After 1.5 h, the reaction was poured onto 50 mL of crushed ice and H2O. A white precipitate developed. EtOAc (50 mL) was added after several hours had passed. Solid NaHCO3 was added portionwise (bubbling) until the aq. layer had a pH of 9. The slurry was extracted with EtOAc (2×25 mL). The combined organic layers were washed with 1.0 M aq. CuSO4 monohydrate (3×25 mL) and H2O (25 mL). The final organic phase was dried over Na2SO4, filtered, and concentrated. The residue was treated with benzene and purified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes) to give (S)-2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropyl acetate. 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J=8.6 Hz, 1H), 7.68 (d, J=7.8 Hz, 1H), 7.52-7.41 (m, 9H), 7.26-7.16 (m, 9H), 5.99 (dd, J=8.2, 4.7 Hz, 1H), 4.02 (app. s, 2H), 3.55 (dd, J=8.6, 8.4 Hz, 1H), 3.12 (dd, J=9.8 Hz, 4.7 Hz, 1H), 2.52 (s, 3H), 1.86 (s, 3H), 1.32 (s, 3H), 1.15 (s, 3H).

Workup

  1. custom(bubbling) until the aq. layer
  2. extractionThe slurry was extracted with EtOAc (2×25 mL)
  3. washThe combined organic layers were washed with 1.0 M aq. CuSO4 monohydrate (3×25 mL) and H2O (25 mL)
  4. dry with materialThe final organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionThe residue was treated with benzene
  8. custompurified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b054d271dfdc4165b7b69846c6b2b339
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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