Methanol → (S)-4-chloro-9-hydroxy-7,7-dimethyl-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3-one

HRID 573791

Reaction equation

HRID 573791 reaction equation
C1C2C(=CC=CC=2)[C@@H](N)[C@H]1O.B.CCN(C1C=CC=CC=1)CC.[Cl:24][C:25]1[C:34]2[C:35](=[O:43])[O:36][C:37]3([CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[C:33]=2[C:32]2[C:31](=[O:44])[CH2:30][C:29]([CH3:46])([CH3:45])[CH2:28][C:27]=2[N:26]=1.CO>O1CCCC1>[Cl:24][C:25]1[C:34]2[C:35](=[O:43])[O:36][C:37]3([CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)[C:33]=2[C:32]2[C@@H:31]([OH:44])[CH2:30][C:29]([CH3:46])([CH3:45])[CH2:28][C:27]=2[N:26]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 83312Diethylaniline-boraneHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanol2×HCID 866625334-chloro-7,7-dimethyl-2',3',5',6',7,8-hexahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3,9(6H)-dione

Product 1

HCID 86662532(S)-4-chloro-9-hydroxy-7,7-dimethyl-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

213 mg (1R,2S)-(+)-cis-1-Amino-2-indanol are dissolved in 250 ml tetrahydrofurane and to this solution are dropwise added 3.58 ml of a borane-diethylaniline-complex. After completion of gas evolution the solution is cooled to 0° C. and 3.17 g 4-chloro-7,7-dimethyl-2′,3′,5′,6′,7,8-hexahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran]-3,9(6H)-dione in 250 ml tetrahydrofurane are added dropwise. The temperature is raised during 2 hours to room temperature and the mixture is stirred for 18 hours, 213 mg (1R,2S)-(+)-cis-1-Amino-2-indanol are added and stirring is continued for further 7 hours. 20 ml methanol are added dropwise and the mixture is stirred for additional 10 minutes. The mixture is partitioned between 0.1 M hydrochloric acid and ethylacetate. The aqueous phase is twice extracted with ethylacetate. The combined organic phases are dried with sodium sulphate and the solvents are evaporated in vacuo. The residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 0:100).

Workup

  1. temperatureThe temperature is raised during 2 hours to room temperature
  2. stirringstirring
  3. waitis continued for further 7 hours
  4. stirringthe mixture is stirred for additional 10 minutes
  5. customThe mixture is partitioned between 0.1 M hydrochloric acid and ethylacetate
  6. extractionThe aqueous phase is twice extracted with ethylacetate
  7. dry with materialThe combined organic phases are dried with sodium sulphate
  8. customthe solvents are evaporated in vacuo
  9. customThe residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 0:100)

Sources & evidence

ORD record
ord-4d4d54b3d1504b99a543e1154d53dc7e
Source dataset
uspto-grants-2015_05
Patent number
US09029544B2

Linked notes

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