Methyl chloroformate → 4-Hydroxymethyl-n-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)benzamide

HRID 473393Notes

Reaction equation

HRID 473393 reaction equation
[CH3:1][C:2]1([CH3:26])[C:7]2[CH:8]=[CH:9][C:10]([NH:12][C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21](O)=[O:22])=[CH:17][CH:16]=3)=[O:14])=[CH:11][C:6]=2[C:5]([CH3:25])([CH3:24])[CH2:4][CH2:3]1.C(N(CC)CC)C.ClC(OC)=O.[BH4-].[Na+].[Cl-].[NH4+]>O1CCCC1.O>[OH:22][CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]([NH:12][C:10]2[CH:9]=[CH:8][C:7]3[C:2]([CH3:26])([CH3:1])[CH2:3][CH2:4][C:5]([CH3:25])([CH3:24])[C:6]=3[CH:11]=2)=[O:14])=[CH:16][CH:17]=1

Participants

8

Reactant 5

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 108143TamibaroteneHCID 4311764Sodium borohydride

Product 1

HCID 684321204-Hydroxymethyl-n-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)benzamideYield 94.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of Am-80 (320 mg, 0.912 mmol) and triethylamine (152 μl, 1.09 mmol) in tetrahydrofuran (5 ml) was cooled to −20° C., and added dropwise with a solution of methyl chloroformate (82 μl, 1.06 mmol) in tetrahydrofuran, and the mixture was stirred for 1 hour. The reaction mixture was filtered through Cerite, and then washed with tetrahydrofuran (3 ml). The filtrate was cooled on ice, and added with NaBH4 (208 mg, 5.47 mmol), then the mixture was slowly added dropwise with water (4 ml) with vigorous stirring, and stirring was further continued over 18 hours until the reaction mixture became 26° C. The reaction mixture was added with saturated aqueous ammonium chloride, the mixture was extracted with ethyl acetate, and the organic layer was treated in a conventional manner. The residue was separated by silica gel chromatography [eluted with hexane-ethyl acetate (2:1)], and recrystallized to obtain 4-hydroxymethyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)benzamide (290 mg, 94%) as colorless prisms.

Workup

  1. filtrationThe reaction mixture was filtered through Cerite
  2. washwashed with tetrahydrofuran (3 ml)
  3. temperatureThe filtrate was cooled on ice
  4. stirringstirring
  5. waitwas further continued over 18 hours until the reaction mixture
  6. custombecame 26° C
  7. extractionthe mixture was extracted with ethyl acetate
  8. additionthe organic layer was treated in a conventional manner
  9. customThe residue was separated by silica gel chromatography [eluted with hexane-ethyl acetate (2:1)]
  10. customrecrystallized

Sources & evidence

ORD record
ord-a8dce6c74f9d497d816f1f80d53d7a87
Source dataset
uspto-grants-2014_01
Patent number
US08633335B2

Reaction notes

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